Sodium-Glucose Cotransporter-2 Inhibitors and Gastrointestinal Neoplasm Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Sodium-Glucose Cotransporter-2 Inhibitors and Gastrointestinal Neoplasm Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Sodium-Glucose Cotransporter-2 Inhibitors and Gastrointestinal Neoplasm Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Yufan Zhang, Jiajie Xie, Qi Wu, Xiaoyu Zhou, Ceng Zeng, Yan Zeng, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9272597/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background The potential carcinogenic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remain controversial, particularly regarding site-specific gastrointestinal (GI) neoplasms. This systematic review and meta-analysis aimed to determine the relationship between SGLT2 inhibitors and the risk of GI neoplasms in patients with T2DM. Materials and methods We searched PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science to March 17, 2025, for RCTs in T2DM comparing SGLT2 inhibitors with placebo or another active comparator. The primary outcome was GI neoplasms; secondary, prespecified site-specific neoplasms (esophageal, gastric, hepatic, pancreatic, colorectal, rectal, biliary). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in Stata 17.0, using fixed- or random-effects models according to the heterogeneity. Prespecified subgroups included agents, dose, exposure duration (≤ 52, 52–104, > 104 weeks), age, body mass index (BMI), and hemoglobin A1c (HbA1c). Publication bias was evaluated with funnel plots and Egger’s test. Results In a pooled analysis of 49 RCTs (n = 49,054), SGLT2 inhibitors therapy was not associated with the overall risk of GI neoplasm (OR = 1.10, 95% CI: 0.84–1.44; p = 0.46; I² = 0%). Site-specific analyses were likewise null for esophageal (OR = 1.12, 95% CI 0.37–3.45), gastric (1.20, 0.65–2.23), hepatic (0.62, 0.31–1.22), pancreatic (0.93, 0.52–1.66), colonic (1.28, 0.78–2.08), colorectal (0.76, 0.27–2.17), and rectal neoplasms (0.98, 0.49–1.97), with all p-values > 0.05. Subgroup analyses by agents (e.g., canagliflozin, dapagliflozin, empagliflozin), baseline age, BMI, HbA1c, treatment duration, and dose were also non-significant (all p > 0.05). Approximately half of the trials had follow-up of one year or less, limiting our ability to evaluate long-term risk. Conclusions This comprehensive meta-analysis indicates that SGLT2 inhibitor therapy is not associated with an increased risk of gastrointestinal neoplasms in patients with T2DM across the follow-up durations evaluated, with consistent findings across pharmacologic subclasses. SGLT2 inhibitors type 2 diabetes gastrointestinal neoplasms meta-analysis canagliflozin empagliflozin dapagliflozin Figures Figure 1 Figure 2 Figure 3 Introduction The global prevalence of diabetes continues to escalate, affecting an estimated 589 million individuals in 2024, with projections reaching 853 million by 2050 (1). Poor glycemic control worsens vascular complications and is increasingly implicated in cancer pathogenesis (2, 3). Type 2 diabetes mellitus (T2DM) increases overall cancer risk by 10–20%, particularly for liver, pancreatic, and colorectal neoplasms, via mechanisms like hyperinsulinemia, insulin resistance, and chronic inflammation (4). The long-term oncogenic implications of antihyperglycemic therapies remain controversial. Observational studies reveal divergent effects: insulin analogs and sulfonylureas may elevate gastrointestinal (GI) neoplasm risk (5), whereas metformin appears protective. In contrast, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists show neutral or inconsistent associations (6, 7). Sodium–glucose cotransporter 2 (SGLT2) inhibitors—now a cornerstone for cardiorenal protection in T2DM (8) —lower glucose via insulin-independent blockade of renal glucose reabsorption, yet their potential carcinogenicity, particularly for GI neoplasms, remains uncertain. Randomized controlled trials (RCTs) provide discordant signals: EMPA-REG OUTCOME reported numerically fewer colorectal cancers with empagliflozin, whereas the CANVAS Program observed more colorectal and pancreatic events with canagliflozin; both findings were statistically non-significant (9, 10). Beyond these largely non-significant estimates, several large outcome trials have demonstrated statistically significant cardiorenal benefits with SGLT2 inhibitors (e.g., reduced heart-failure hospitalization and slower chronic kidney disease progression), prompting guideline-level uptake and sharpening the need to clarify long-term oncologic safety under real-world exposure. Program-level safety summaries have also noted site-specific, sometimes nominally significant, imbalances (e.g., colorectal/pancreatic events in canagliflozin programs; fewer colorectal events with empagliflozin (11)) that have not been consistent across agents or replicated across programs (12). Moreover, real-world cohorts have reported statistically significant associations—for example, a lower gastric cancer incidence versus DPP-4 inhibitors (adjusted HR ≈ 0.30) and reduced risks across several GI sites—that contrast with neutral RCT results (13). Collectively, these mixed signals underscore both the clinical relevance and evidentiary uncertainty motivating our trial-based meta-analysis of GI neoplasms across agents, doses, and exposure windows. The relationship between SGLT2 inhibitor use and gastrointestinal neoplasm risk in T2DM remains inadequately defined, especially regarding dose–response, treatment duration, and effect modification by patient characteristics. To address this gap, we conducted the first systematic meta-analysis to comprehensively evaluate the association between SGLT2 inhibitor therapy and GI neoplasms incidence, including esophageal, gastric, pancreatic, hepatic, colonic, colorectal, rectal, and biliary tract neoplasms. Furthermore, stratified subgroup analyses were performed to explore potential confounding effects of key variables, including treatment dosage, duration, mean age, and body mass index (BMI). Through this quantitative synthesis, our study aims to elucidate the safety profile of SGLT2 inhibitors in clinical practice and provide robust evidence to guide therapeutic decision-making. Methods The protocol for this systematic review and meta-analysis was registered with PROSPERO (CRD42024619019). The review followed the PRISMA 2020 reporting guidelines (14), ensuring methodological transparency and adherence to contemporary standards for evidence synthesis. The completed PRISMA 2020 checklist is available in Supplementary Appendix 1. Search Strategy We systematically searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus for randomized controlled trials (RCTs) of SGLT2 inhibitors in people with type 2 diabetes from database inception to March 17, 2025. Additionally, we searched for unpublished and ongoing trials in ClinicalTrials.gov, manually reviewed the reference lists of relevant systematic reviews and meta-analyses, and examined grey literature available in clinical trial registries, without language restrictions. Following initial identification, we performed full-text screening of all records that covered SGLT2 inhibitors and/or GI neoplasms and included relevant studies in this section at the appropriate point. The search encompassed all SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) compared to placebo or active glucose-lowering agents (e.g., metformin, insulin) to assess GI neoplasms incidence during follow-up. The search strategy combined terms for SGLT2 inhibitors (e.g., *sodium-glucose cotransporter 2 inhibitor*, canagliflozin) and GI neoplasms (e.g., colorectal neoplasms, hepatocellular carcinoma), with full syntax provided in Supplementary Appendix 2. Two investigators independently screened titles/abstracts and assessed full texts for eligibility, with discrepancies resolved by consensus or a third reviewer. To minimize publication bias, search terms were not restricted to specific cancer-related vocabulary. Full texts and supplementary materials were comprehensively reviewed to identify unreported outcomes. Study Selection Studies that fulfill the following criteria were encompassed in this meta-analysis: (1) participants were T2DM patients; (2) follow-up period ≥ 24 weeks; (3) the experimental group was provided SGLT2 inhibitor therapy (monotherapy or combination regimens), and the control group received placebo or non-SGLT2 glucose-lowering therapies; (4) reported GI neoplasms outcomes in publications or trial registries (e.g., ClinicalTrials.gov). Exclusion criteria: (1) non-RCTs, including reviews, case-control studies, cross-sectional studies, and case reports; (2) patients with type 1 diabetes mellitus or non-diabetic individuals; (3) non-English publications; (4) duplicate reports (Supplementary Appendix 3). For studies with multiple publications, the version with the longest follow-up or most complete data was selected. Two investigators independently screened eligible studies, with discrepancies resolved through consensus or consultation with a third reviewer. Data Extraction and Quality Assessment Data were extracted independently by two researchers and reviewed by a third researcher. The extracted data comprised: (1) study characteristics, such as author, region, year of publication, and treatment duration; (2) participant characteristics, including age, sex, sample size, diabetes duration, body mass index, hemoglobin A1c (HbA1c) and fasting blood glucose concentrations; (3) total number of GI neoplasms; (4) drug name and dose utilized by the experimental and control groups (Supplementary Appendix 4 for details). For the incidence of GI neoplasms, the total number of participants in both the experimental and control groups was estimated. If multiple publications from the same study population were identified, the report with the longest follow-up duration and most complete data was selected. RCTs were assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. The evaluation criteria include review and judgment of “low risk,” “high risk,” or “unclear risk” in terms of sequence generation, allocation concealment, blinding, incomplete outcome data, as well as selective outcome reporting, and free of other bias (Supplementary eFigure 1). Yu-Fan Zhang independently assessed the risk of bias and compiled detailed descriptions of all studies. Statistical Analysis Statistical analyses were performed using Stata 17.0 (StataCorp LLC). The odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to quantify associations. Heterogeneity was quantified with I². When I² < 50%, fixed-effects models were applied; otherwise, random-effects models were used. Two-sided p < 0.05 indicated statistical significance; p < 0.10 was considered suggestive in prespecified subgroup analyses. Subgroup definitions Prespecified subgroups and their cut points were chosen a priori on biological and methodological grounds. Exposure duration was categorized as ≤ 52, 52–104, and > 104 weeks, consistent with prior SGLT2 meta-analyses evaluating malignancy risk and intended to approximate short-, intermediate-, and extended exposure windows relevant to oncologic latency (15). Glycemic control was stratified by baseline HbA1c ≤ 8.0% vs > 8.0%, consistent with the 2024 ADA Standards of Care, which endorse less stringent glycemic goals (< 8.0%) for many adults and that are widely used to demarcate poorer control in trials (16). Adiposity followed established adult BMI categories (overweight: 25 ≤ BMI < 30 kg/m²; obesity: BMI ≥ 30 kg/m²) (17, 18). Dose was classified as FDA-labeled low (starting) vs high (maximum approved) for each agent (e.g., empagliflozin 10/25 mg; dapagliflozin 5/10 mg; canagliflozin 100/300 mg; ertugliflozin 5/15 mg); for agents approved outside the U.S., we used the corresponding national labels (e.g., tofogliflozin 20 mg; luseogliflozin 2.5–5 mg). Results Eligible Studies and Characteristics A total of 2,791 citations were initially identified, and 356 full-text articles were assessed for eligibility. Based on the search strategy, 49 RCTs (19–67) encompassing 41 articles involving 49,054 participants met the eligibility criteria (Fig. 1 ). Of these, 28,651 participants were randomized to intervention groups receiving SGLT2 inhibitors, including ertugliflozin, bexagliflozin, dapagliflozin, empagliflozin, canagliflozin, tofogliflozin, and luseogliflozin. The included trials spanned multiple countries, with sample sizes ranging from 138 to 6,609 participants. Intervention durations varied between 24 weeks and 338 weeks. The mean baseline age of participants was 60.20 years (standard deviation [SD] 8.70), with 64.1% male. At baseline, the mean BMI was 30.80 kg/m² (SD 5.80) and HbA1c was 8.17% (SD 0.97). Detailed participant characteristics are summarized in Table 1 . Methodological quality assessment of the included studies, including descriptions of randomization and double-blinding procedures, is provided in Supplementary Appendix 5. The majority of studies demonstrated robust methodological rigor, with clear reporting of trial protocols. Table 1 Baseline characteristics of randomized controlled clinical trials and participants included. Study Inclusion Period Follow up Randomised treatments Duration of diabetes. (Mean. SD). years Total cases Completed cases Age (mean. SD). years No. (%) of male Weight (mean. SD). kg BMI (mean. SD). kg/m 2 FPG (mmol/l) HbA1c (mean. SD). % No. (%) of White No. (%) of Black or African American No. (%) of Asian No. (%) of Others Strojek K 2011 Apr 2008 to Nov 2009 24 weeks Placebo Dapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg 7.4 (5.7) 7.7 (6.0) 7.4 (5.7) 7.2 (5.5) 145 154 142 151 133 140 132 141 60.3 (10.2) 59.9 (10.1) 60.2 (9.7) 58.9 (8.3) 71 (49.0) 77 (50.0) 71 (50.0) 66 (43.7) 29.7 (4.6) 30.0 (5.1) 29.8 (5.2) 29.8 (5.6) 29.7 (4.6) 30.0 (5.1) 29.8 (5.2) 29.8 (5.6) 9.6 (2.1) 9.6 (2.1) 9.7 (2.1) 9.6 (2.0) 8.2 (0.7) 8.1 (0.8) 8.1 (0.8) 8.1 (0.7) 101 108 96 106 0 45 46 46 45 0 NCT01095653 2012 Mar 26, 2010 to March 2012 24 weeks Placebo Dapagliflozin 5 mg Dapagliflozin 10 mg NR 132 128 133 113 113 117 49.9 (10.9) 53.0 (11.1) 51.2 (9.9) 87 (65.9) 84 (65.6) 86 (64.7) 72.2 (13.2) 68.9 (11.4) 70.9 (11.6) 25.9 (3.6) 25.2 (3.3) 25.8 (3.4) NR NR 0 0 132 (100.0) 128 (100.0) 133 (100.0) 0 Lavalle-González FJ 2013 Apr 2010 to Aug 2012 52 weeks Placebo Sitagliptin 100 mg Canagliflozin 100 mg Canagliflozin 300mg. 6.8 (5.3) 6.8 (5.2) 6.7 (5.4) 7.1 (5.4) 183 366 368 367 155 319 322 323 55.3 (9.8) 55.5 (9.6) 55.5 (9.4) 55.3 (9.2) 94 (51.4) 172 (47.0) 174 (47.3) 165 (45.0) 86.6 (22.4) 87.7 (21.6) 88.8 (22.2) 85.4 (20.9) 31.1 (6.1) 32.0 (6.1) 32.4 (6.4) 31.4 (6.3) 9.1 (2.1) 9.4 (2.3) 9.3 (2.3) 9.6 (2.5) 8.0 (0.9) 7.9 (0.9) 7.9 (0.9 7.9 (0.9) 129 (70.5) 264 (72.1) 252 (68.5) 256 (69.8) 3 (1.6) 13 (3.6) 16 (4.3) 13 (3.5) 30 (16.4) 41 (11.2) 51 (13.9) 60 (16.3) 21 (11.5) 48 (13.1) 49 (13.3) 38 (10.4) Barnett AH 2014 Sept 3, 2010. and Jul 26, 2012 52 weeks Placebo Empagliflozin 10 mg Empagliflozin 25 mg NR 319 98 321 278 88 280 64.1 (8.7) 63.2 (8.5) 63.9 (9.0) 181 (56.7) 60 (61.2) 189 (58.9) 83.4 (19.0) 92.1 (21.4) 84.1 (20.1) 30.6 (5.5) 32.4 (5.4) 30.4 (5.4) 8.0 (2.7) 8.1 (1.9) 8.1 (2.1) 8.1 (0.8) 8.0 (0.8) 8.0 (0.8) 191 (59.9) 69 (70.4) 185 (57.6) 6 (1.9) 3 (3.1) 13 (4.0) 119 (37.3) 25 (25.5) 122 (38.0) 3 (0.9) 1 (1.0) 1 (0.4) Kaku K 2014 Oct 30, 2010 and Feb 28, 2012 24 weeks Placebo Tofogliflozin 10mg Tofogliflozin 20mg Tofogliflozin 40mg 6.0 (6.1) 6.3 (7.1) 6.4 (5.1) 6.7 (5.5) 56 57 58 58 48 54 56 54 56.8 (9.9) 58.6 (9.8) 56.6 (10.2) 57.0 (9.1) 37 (66.1) 38 (66.7) 39 (67.2) 39 (67.2) 71.2 (12.6) 67.3 (12.7) 68.1 (15.8) 68.7 (11.9) 26.0 (4.1) 25.1 (3.5) 25.0 (4.6) 25.8 (4.1) 9.4 (1.4) 9.5 (1.8) 9.4 (1.6) 9.3 (2.1) 8.4 (0.8) 8.5 (0.8) 8.3 (0.8) 8.3 (0.8) NR NR NR NR Leiter LA 2014 Mar 15, 2010 to May 30, 2011 24 weeks Placebo Dapagliflozin 10 mg QD.PO 13.0 (8.4) 13.5 (8.2) 480 482 441 428 63.6 (7.0) 63.9 (7.6) 323 (67.0) 321 (66.9) 93.2 (16.8) 94.5 (17.8) 32.7 (5.7) 33.0 (5.3) 9.2 (2.5) 9.0 (2.6) 8.1 (0.8) 8.0 (0.8) 454 (94.6) 449 (93.2) 9 (1.9) 10 (2.1) 6 (1.3) 7 (1.5) 11 (2.3) 16 (3.3) Ji L 2014 Jun 2010 to Mar 2012 24 weeks Placebo Dapagliflozin5mg Dapagliflozin10mg 1.3 (2.0) 1.2 (2.3) 1.7 (2.8) 132 128 133 113 113 117 49.9 (10.9) 53.0 (11.1) 51.2 (9.9) 87 (65.9) 84 (65.6) 86 (64.7) 72.2 (13.2) 68.9 (11.4) 70.9 (11.6) 25.9 (3.6) 25.2 (3.3) 25.8 (3.4) 9.3 (2.4) 8.6 (1.8) 9.0 (2.4) 8.4 (1.0) 8.1 (0.7) 8.3 (1.0) 0 0 132 128 133 0 Rosenstock J 2014 Mar 2011 to Apr 2013 52 weeks Placebo Empagliflozin 10 mg Empagliflozin 25 mg NR 189 187 190 161 159 168 55.3 (10.1) 56.7 (8.7) 58.0 (9.4) 75 (39.9) 97 (52.2) 84 (44.4) 95.5 (17.5) 96.7 (17.9) 95.9 (17.3) 34.7 (4.3) 34.7 (3.8) 35.0 (4.0) 8.4 (2.5) 8.8 (2.7) 8.3 (2.7) 8.3 (0.1) 8.4 (0.1) 8.3 (0.1) 174 (93) 175 (94) 182 (96) 8 (4) 7 (4) 4 (2) 0 0 0 6 (3) 4 (2) 3 (2) Nauck MA 2014 Mar 31, 2008 to Dec 15, 2009 52 weeks Dapagliflozin (2.5. 5. or 10 mg) Glipizide (5. 10. or 20 mg) NR 406 408 322 314 58.1 (9.4) 58.6 (9.8) 221 (55.3) 220 (54.9) NR 31.7 (5.1) 31.2 (5.1) 9.0 (2.1) 9.1 (2.3) 7.7 (0.9) 7.7 (0.9) 327 (81.8) 323 (80.6) 26 (6.5) 24 (6.0) 27 (6.8) 34 (8.5) 20 (5.0) 20 (5.0) Ridderstråle M 2014 Aug 2010 to Jun 2011. 104 weeks Empagliflozin 25mg glimepiride 1–4 mg NR 769 780 610 589 55.7 (10.4) 56.2 (10.3) 421 (54.0) 432 (56.5) 83.0 (19.2) 82.5 (19.2) 30.3 (5.3) 30.0 (5.3) 8·32 (1·98) 8·32 (1·77) 7.92 (0.86) 7.92 (0.81) 519 (66.5) 498 (65.1) 8 (1.0) 12 (1.6) 253 (32.4) 254 (33.2) 0 1 (< 1%) Inagaki N 2014 Jul 2011 to Aug 2012 24 weeks Placebo Canagliflozin 100 mg Canagliflozin 200 mg 5.6 (5.8) 4.7 (4.6) 5.9 (5.9) 93 90 89 74 84 83 58.2 (11.0) 58.4 (10.4) 57.4 (11.1) 60 (64.5) 59 (65.6) 72 (81.8) 68.6 (15.2) 69.1 (14.5) 69.9 (14.2) 25.9 (4.4) 25.6 (4.2) 25.4 (4.2) 9.1 (1.8) 8.8 (2.0) 9.2 (1.9) 8.0 (0.7) 8.0 (0.7) 8.0 (0.8) 0 0 93 (100.0) 90 (100.0) 88 (100.0) 0 Wilding JP 2014 Apr 30, 2008 to May 19, 2009 24 weeks Placebo Dapagliflozin2.5mg Dapagliflozin5/10mg Dapagliflozin10mg 13.5 (7.3) 13.6 (6.6) 13.1 (7.8) 14.2 (7.3) 193 202 211 194 168 180 186 178 58.8 (8.6) 59.8 (7.6) 59.3 (7.9) 59.3 (8.8) 98 (50.8) 102 (50.5) 111 (52.6) 107 (55.2) 94.5 (19.8) 93.0 (16.7) 93.3 (17.4) 94.5 (16.8) 33.1 (5.9) 33.0 (5.0) 33.0 (5.3) 33.4 (5.1) 9.5 (3.2) 10.0 (3.3) 10.3 (3.3) 9.6 (3.0) 8.5 (0.8) 8.5 (0.8) 8.6 (0.9) 8.6 (0.8) 186 (96.4) 190 (94.1) 200 (94.8) 184 (94.8) 6 (3.1) 3 (1.5) 5 (2.4) 5 (2.6) 0 7 (3.5) 3 (1.4) 3 (1.5) 1 (0.5) 2 (1.0) 3 (1.4) 2 (1.0) Bailey CJ 2015 Jun 7, 2010 to May 23, 2013 26 weeks Placebo Canagliflozin 100 mg Canagliflozin 300 mg 11.4 (7.3) 12.3 (7.8) 11.3 (7.2) 237 241 236 158 184 178 63.2 (6.2) 64.3 (6.5) 63.4 (6.0) 143 (60.3) 124 (51.5) 129 (54.7) 91.1 (17.5) 88.4 (15.6) 88.8 (17.1) 31.8 (4.8) 31.4 (4.4) 31.5 (4.6) 8.7 (2.2) 8.9 (2.2) 8.5 (2.0) 7.8 (0.8) 7.8 (0.8) 7.7 (0.8) 185 (78.1) 194 (80.5) 173 (73.3) 20 (8.4) 18 (7.5) 19 (8.1) 21 (8.9) 15 (6.2) 25 (10.6) 11 (4.6) 14 (5.8) 19 (8.1) J Rosenstock 2015 Nov 2009 to May 2012 78 weeks Placebo Empagliflozin 10 mg Empagliflozin 25 mg NR 170 169 155 147 153 129 58.1 (9.4) 58.6 (9.8) 59.9 (10.5) 90 (53) 93 (55) 93 (60) 90.5 (1.7) 91.6 (1.5) 94.7 (1.7) 31.8 (6.0) 32.1 (5.8) 32.7 (5.9) 7.9 (0.2) 7.7 (0.2) 8.1 (0.2) 8.1 (0.1) 8.3 (0.1) 8.3 (0.1) 113 (66) 119 (70) 111 (72) 21 (12) 12 (7) 15 (10) 33 (19) 37 (22) 28 (18) 3 (2) 1 (1) 1 (1) Roden M 2015 Feb 2011 to May 2013 24 weeks Placebo Empagliflozin 10 mg Empagliflozin 25 mg Sitagliptin 100 mg NR 228 224 224 223 119 147 143 136 54.9 (10.9) 56.2 (11.6) 53.8 (11.6) 55.1 (9.9) 123 (53.9) 142 (63.4) 145 (64.7) 141 (63.2) 78.2 (19.9) 78.4 (18.7) 77.8 (18.0) 79.3 (20.4) 28.7 (6.2) 28.3 (5.5) 28.2 (5.5) 28.2 (5.2) 8.6 (2.0) 8.5 (1.8) 8.5 (1.9) 8.2 (1.6) 7.9 (0.8) 7.9 (0.9) 7.9 (0.9) 7.9 (0.8) 76 (33.3) 77 (34.4) 73 (32.6) 76 (34.1) 6 (2.6) 3 (1.3) 7 (3.1) 3 (1.3) 146 (64.0) 143 (63.8) 144 (64.3) 143 (64.1) 0 1 (0.4) 0 1 (0.4) Rosenstock Julio 2015 Jul 2012 to Jan 2014 24 weeks Saxagliptin 5mg and Dapagliflozin 10mg plus MET Saxagliptin 5mg and Placebo plus MET Dapagliflozin 10mg and Placebo plus MET 7.6 (5.3) 179 176 179 161 160 169 53 (10) 55 (10) 54 (10) 94 (53.4) 89 (49.7) 85 (47.5) 87.1 (18.0) 88.0 (18.7) 86.3 (18.6) 31.8 (4.8) 31.8 (5.1) 31.5 (5.3) 10 (2.53) 10.7 (2.5) 10.3 (2.7) 8.92 (1.18) 9.03 (1.05) 8.87 (1.16) 120 (67.0) 121 (68.7) 131 (73.2) 22 (12.3) 22 (12.5) 16 (8.9) 12 (6.7) 11 (6.3) 10 (5.6) 25 (14.0) 22 (12.5) 22 (12.3) Rosenstock J 2016 May 16, 2013 to Dec 1,2014 26 weeks Metformin XR Canagliflozin 100 mg Canagliflozin 300 mg Canagliflozin 100 mg + Metformin XR Canagliflozin 300 mg + Metformin XR 3.3 (4.5) 3.5 (4.4) 3.3 (4.4) 2.9 (3.3) 3.3 (3.9) 237 237 238 237 237 205 211 216 225 212 55.2 (9.8) 54.0 (10.7) 55.8 (9.6) 54.2 (9.7) 55.4 (9.8) 116 (48.9) 105 (44.3) 125 (52.5) 108 (45.6) 115 (48.5) 92.1 (20.1) 90.2 (18.6) 93.0 (19.9) 88.3 (17.6) 91.4 (21.4) 33.0 (6.0) 32.4 (5.4) 32.6 (5.8) 31.9 (5.3) 32.8 (6.5) 10.6 (2.7) 10.9 (3.0) 10.7 (2.9) 10.6 (2.8) 11.2 (3.1) 8.8 (1.2) 8.8 (1.2) 8.8 (1.2) 8.8 (1.1) 8.8 (1.2) 192 (81.0) 192 (81.0) 208 (87.4) 189 (79.7) 187 (78.9) 9 (3.8) 12 (5.1) 8 (3.4) 6 (2.5) 8 (3.4) 9 (3.8) 4 (1.7) 4 (1.7) 6 (2.5) 5 (2.1) 27 (11.4) 29 (12.2) 18 (7.6) 36 (15.2) 37 (15.6) Haneda M 2016 May 2011 to October 2012 52 weeks Placebo Luseogliflozin 2.5 or 5mg 12.6 (10.4) 10.4 (6.9) 50 95 45 83 68.4 (8.9) 67.9 (8.9) 39 (78.0) 72 (75.8) 67.8 (11.8) 66.9 (13.6) 25.8 (4.0) 25.5 (4.2) 7.9 (1.5) 7.8 (1.7) 7.7 (0.7) 7.7 (0.7) NR NR NR NR Kadowaki T 2017 Jan 2015 to Jan 2016 24 weeks Placebo + Teneligliptin 20 mg Canagliflozin 100 mg + Teneligliptin 20 mg 6.5 (3.9) 8.3 (7.7) 68 70 61 67 56.0 (9.5) 58.4 (8.9) 53 (77.9) 54 (77.1) 73.3 (12.9) 71.3 (15.9) 26.4 (3.9) 25.5 (4.2) 9.2 (1.9) 9.7 (1.7) 7.9 (0.8) 8.2 (0.9) NR NR NR NR Pratley RE 2017 Apr 22,2014 to May 26,2016 52 weeks Ertugliflozin 5 mg Ertugliflozin 15 mg Sitagliptin 100 mg Ertugliflozin 5 mg + Sitagliptin 100 mg Ertugliflozin 15 mg + Sitagliptin 100 mg 7.1 (5.4) 7.3 (5.4) 6.2 (5.2) 7.0 (5.6) 6.9 (5.2) 250 248 247 243 245 226 217 219 221 218 55.1 (10.1) 55.3 (9.5) 54.8 (10.7) 55.2 (10.4) 55.1 (9.8) 127 (50.8) 134 (54.0) 154 (62.3) 123 (50.6) 126 (51.6) 88.6 (22.2) 88.0 (20.3) 89.8 (23.5) 89.5 (20.8) 87.5 (20.5) 31.8 (6.2) 31.5 (5.8) 31.7 (6.5) 32.5 (6.7) 31.8 (6.5) 10.23 (2.9) 9.97 (2.54) 9.69 (2.59) 10.21(2.46) 9.84 (2.74) 8.6 (1.0) 8.6 (1.0) 8.5 (1.0) 8.6 (1.0) 8.6 (1.0) 7 (2.8) 4 (1.6) 4 (1.6) 2 (0.8) 4 (1.6) 7 (2.8) 6 (2.4) 11 (4.5) 12 (4.9) 10 (4.1) 22 (8.8) 22 (8.9) 29 (11.7) 22 (9.1) 36 (14.8) 8 (3.2) 11 (4.4) 10 (3.6) 10 (4.1) 6 (2.5) Terra SG 2017 Oct 9, 2013 to Jul 28, 2016 52 weeks Placebo Ertugliflozin 5 mg Ertugliflozin 15 mg 4.6 (4.5) 5.1 (5.1) 5.2 (5.6) 153 156 152 121 137 128 56.1 (10.9) 56.8 (11.4) 56.2 (10.8) 82 (53.6) 89 (57.1) 90 (59.2) 94.2 (25.2) 94.0 (25.4) 90.6 (18.3) 33.3 (6.8) 33.2 (7.4) 32.5 (5.7) 10.0 (2.5) 10.0 (2.7) 9.9 (2.7) 8.1 (0.9) 8.2 (0.9) 8.4 (1.1) 126 (82.4) 134 (85.9) 126 (82.9) 9 (5.9) 10 (6.4) 10 (6.6) 15 (9.8) 10 (6.4) 14 (9.2) 3 (2.0) 2 (1.3) 2 (1.3) CANVAS-R 2018 Jan 16, 2014 to Feb 23,2017 156 weeks Placebo Canagliflozin 100 and 300 mg NR 2905 2907 2866 2872 64.0 (8.3) 63.9 (8.4) 1794 (61.8) 1854 (63.8) NR NR NR NR 2372 (81.7) 2393 (82.3) 125 (4.3) 106 (3.6) 245 (8.4) 244 (8.4) 245 (5.7) 164 (5.6) CANVAS 2018 Dec 9, 2009 to Feb 22, 2017 338 weeks Placebo Canagliflozin 100 mg Canagliflozin 300 mg NR 1442 1445 1443 1297 1344 1441 62.3 (8.0) 62.2 (8.0) 62.8 (8.1) 956 (66.3) 961 (66.5) 944 (65.4) NR NR NR NR 1064 (73.8) 1060 (73.4) 1055 (73.1) 35 (2.4) 32 (2.2) 38 (2.6) 262 (18.2) 270 (18.7) 263 (18.2) 81 (5.6) 83 (5.7) 87 (8.2) CREDENCE,2018 Feb 17, 2014 to Oct 30, 2018 240 weeks Placebo Canagliflozin 100 mg NR 2199 2202 2174 2187 63.2 (9.23) 62.9 (9.17) 1467 (66.7) 1440 (65.4 NR NR NR NR 1436 (65.3) 1476 (67.0) 112 (5.1) 112 (5.1) 452 (20.6) 425 (19.3) 199 (9.0) 189 (8.6) Rosenstock J 2018 Dec 13, 2013 to Aug 3, 2017 26 weeks Placebo Ertugliflozin 5 mg Ertugliflozin 15 mg 8.0 (6.3) 7.9 (6.1) 8.1 (5.5) 209 207 205 175 187 180 56.5 (8.7) 56.6 (8.1) 56.9 (9.4 98 (46.9) 97 (46.9) 93 (45.4) 84.5(17.1) 84.8(17.2) 85.3(16.5) 30.7 (4.7) 30.8 (4.8) 31.1 (4.5) 9.4 (2.3) 9.3 (2.5) 9.3 (2.5) 8.2 (0.9) 8.1 (0.9) 8.1 (0.9) 144 (68.9) 134 (64.7) 133 (64.9) 19 (9.1) 22 (10.6) 23 (11.2) 31 (14.8) 34 (16.4) 35 (17.1) 15 (7.2) 17 (8.2) 14 (6.8) Scott R 2018 Oct 21, 2015 to Oct 10, 2017 24 weeks Sitagliptin 100 mg Dapagliflozin 5–10 mg 10.5 (7.0) 10.7 (7.4) 307 306 299 296 67.7 (8.5) 66.6 (8.6) 169 (55.0) 186 (60.8) 87.4 (20.2) 88.7 (18.0) 31.8 (5.7) 31.5 (5.3) 9.0 (2.2) 9.2 (2.3) 7.7 (0.7) 7.8 (0.7) 240 (78.2) 234 (76.5) 8 (2.6) 11 (3.6) 11 (3.6) 7 (2.3) 48 (15.7) 54 (17.6) Yang W 2018 Mar 31,2014 to Jan 28,2016 24 weeks Placebo + Insulin Dapagliflozin 10 mg QD.PO + Insulin 12.2 (6.7) 12.7 (7.2) 129 139 125 135 58.6 (8.9) 56.5 (8.4) 64 (48.1) 66 (47.5) 72.4 (13.1) 71.1 (12.0) 26.7 (3.3) 26.4 (3.8) 9.3 (2.2) 10.0 (2.6) 8.6 (0.8) 8.5 (0.8) 1 (0.8) 0 0 0 132 (99.2) 137 (98.5) 0 2 (1.4) Hollander P 2019 Dec 16, 2013 to Apr 18, 2017 104 weeks Ertugliflozin 5mg Ertugliflozin 15mg Glimepiride 7.3 (5.7) 7.5 (5.7) 7.6 (5.6) 445 435 435 339 340 327 58.7 (9.8) 58.0 (9.9) 57.9 (9.1) 227 (51.0) 191 (43.9) 224 (51.5) 88.0 (19.0) 85.7 (19.1) 86.9 (20.8) 31.7 (5.6) 31.3 (6.2) 31.2 (6.4) 9.0 (1.9) 9.0 (2.0) 8.8 (1.9) 7.8 (0.6) 7.8 (0.6) 7.8 (0.6) 329 (73.9) 311 (71.5) 317 (72.9) 17 (3.8) 19 (4.4) 25 (5.7) 81 (18.2) 85 (19.5) 72 (16.6) 18 (4.0) 20 (4.6) 21 (4.8) Rodbard HW 2019 Aug 10, 2016 to Mar 8, 2018 26 weeks Semaglutide 14 mg Empagliflozin 25 mg 7.2 (5.8) 7.7 (6.3) 411 410 400 387 57.0 (10.0) 58.0 (10.0) 205 (49.9) 201 (49.0) 91.9 (20.5) 91.3 (20.1) 32.9 (6.3) 32.8 (5.9) 9.5 (2.3) 9.7 (2.5) 8.1 (0.9) 8.1 (0.9) 355 (86.4) 353 (86.1) 26 (6.3) 33 (8.0) 28 (6.8) 21 (5.1) 2 (0.5) 3 (0.7) Ji L 2019 Dec 16, 2015 to Dec 27, 2017 26 weeks Placebo Ertugliflozin5mg Ertugliflozin15mg 6.4 (5.1) 7.0 (5.0) 7.5 (5.1) 167 170 169 157 163 160 56.9 (9.0) 56.1 (9.0) 56.3 (9.3) 88 (52.7) 95 (55.9) 98 (58.0) 70.1 (12.4) 71.4 (11.1) 69.5 (10.9) 26.1 (3.4) 26.0 (2.8) 25.7 (3.2) 9.2 (2.1) 9.4 (2.0) 9.3 (2.3) 8.1 (1.0) 8.1 (0.9) 8.1 (0.9) 0 0 0 0 0 0 167 (100.0) 170 (100.0) 169 (100.0) 0 0 0 Halvorsen YD 2019 Oct 12, 2017 to Oct 31, 2018 24 weeks Bexagliflozin 20 mg. Sitagliptin 100 mg. 8.22 (5.7) 9.36 (5.7) 191 193 180 189 59.3 (9.7) 59.6 (9.8) 120 (62.8) 126 (65.3) 90.3 (20.7) 89.4 (19.0) 32.1 (6.1) 31.4 (5.3) 9.8 (2.3) 10.0 (2.6) 7.9 (0.8) 8.0 (0.9) 158 (82.7) 156 (80.8) 6 (3.1) 2 (1.0) 27 (14.1) 35 (18.1) 0 0 Fuchigami A 2020 July 2017 to June 2018 24 weeks Dapaglifozin 5.0–10mg Sitagliptin 50–100 mg 6.0 (6.4) 5.6 (5.8) 170 170 168 163 58.3 (12.4) 57.9 (12.1) 104 (61.9) 95 (58.3) 74.5 (13.4) 74.9 (15.0) 27.8 (4.0) 27.9 (4.2) 8.4 (1.86) 8.4 (1.71) 7.8 (0.8) 7.8 (0.8) 0 0 0 0 170 (100.0) 170 (100.0) 0 0 Katakami N 2020 Jan 12, 2016. and Nov 25, 2016. 104 weeks Tofoglifozin 20 mg use drugs other than SGLT2 inhibitors 12.1 (8.4) 12.5 (8.3) 169 170 140 147 61.3 (9.3) 60.9 (9.7) 99 (58.6) 99 (58.2) NR 27.0 (5.8 27.0 (4.6 7.8 (1.7) 7.8 (1.8) 7.4 (0.7) 7.3 (0.7) NR NR NR NR Jabbour SA 2020 Sept 4, 2014 to Dec 28, 2017 104 weeks Exenatide 2mg plus Dapagliflozin 10 mg exenatide 2mg plus Placebo Dapagliflozin 10mg 7.6 (6.0) 7.4 (5.5) 7.1 (5.5) 233 231 231 155 154 136 53.8 (9.8) 54.2 (9.6) 54.5 (9.2) 102 (44.7) 116 (51.1) 110 (47.8) 91.8 (22.2) 89.8 (20.2) 91.1 (19.7) 33.2 (6.8) 32.0 (5.9) 33.0 (6.1) 11.0 (3.0) 10.7 (2.8) 10.6 (2.6) 9.3 (1.1) 9.3 (1.1) 9.3 (1.0) 190 (83.3) 194 (85.5) 189 (82.2) 34 (14.9) 27 (11.9) 33 (14.3) 3 (1.3) 1 (0.4) 1 (0.4) 96 (42.1) 96 (42.3) 92 (42.0) Allegretti AS 2021 Sept 23, 2016 to Jan 11, 2018 24 weeks Placebo Bexagliflozin 20 mg NR 155 157 144 152 69.9 (8.3) 69.3 (8.4) 104 (67.1) 92 (58.6) NR NR NR NR 88 (56.8) 83 (52.9) 6 (3.9) 9 (5.7) 59 (38.1) 61 (38.9) 2 (1.3) 4 (2.5) BEST 2021 Oct 12, 2015 to Oct 23, 2019 52 weeks Placebo Bexagliflozin 20 mg 15.2 (9.3) 14.9 (8.6) 567 1133 482 987 64.6 (8.0) 64.4 (8.0) 390 (68.8) 792 (69.9) 92.6 (20.0) 94.6 (21.9) 32.2 (5.8) 32.8 (6.1) NR 8.3 (1.0) 8.3 (0.9) 430 (75.8) 879 (77.6) 28 (4.9) 46 (4.1) 55 (9.7) 108 (9.5) 54 (9.5) 100 (8.8) SOTA-BONE 2021 Feb 19, 2018 to May 30, 2020 2 weeks Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg 104 weeks 126 125 125 9 9 9 66.3 (5.7) 66.1 (6.7) 66.5 (6.9) 70 (55.6) 69 (55.2) 70 (56.0) NR NR NR 8.4 (0.9) 8.3 (0.9) 8.3 (0.9) 88 (69.8) 87 (69.6) 88 (70.4) 8 (6.3) 8 (6.4) 6 (4.8) 26 (20.6) 25 (20.0) 24 (19.2) 4 (3.1) 5 (4.0) 7 (5.6) NCT02769481 2021 Aug 15, 2016 to Jun 14, 2019 NR Bexagliflozin 20 mg Glimepiride 2, 4 or 6 mg 96 weeks 213 213 180 177 59.5 (9.1) 59.7 (10.4) 118 (55.4) 130 (61.0) 88.0 (19.1) 90.2 (17.6) 31.5 (4.9) 32.2 (5.2) NR NR 198 (93.0) 204 (95.8) 5 (2.3) 4 (1.9) 9 (4.2) 4 (1.9) 1 (0.5) 1 (0.5) NCT02926950 2021 Nov 1, 2016 to Mar 22, 2019 4 weeks Placebo + Metformin Sotagliflozin 400 mg + Metformin 79 weeks 259 259 210 211 59.9 (9.4) 60.0 (10.1) 146 (56.4) 142 (54.8) NR NR NR 8.2 (0.8) 8.2 (0.8) 197 (76.1) 223 (86.1) 40 (15.4) 28 (10.8) 19 (7.3) 6 (2.3) 3 (1.2) 2 (0.8) NCT03066830 2021 Feb 24, 2017 to Apr 30, 2019 4 weeks Placebo Sotagliflozin 400 mg 26 weeks 254 253 221 231 63.0 (9.9) 63.3 (8.8) 130 (51.2) 149 (58.9) NR NR NR 8.18 (0.83) 8.20 (0.83) 211 (83.1) 215 (85.0) 8 (3.1) 8 (3.2) 34 (13.4) 28 (11.1) 1 (0.4) 2 (0.8) SOTA-GLIM 2021 Dec 1, 2017 to Sept 6, 2019 2 weeks Placebo Sotagliflozin 400 mg Sotagliflozin 200 mg Glimepiride 52 weeks 159 317 160 318 125 266 128 270 58.8 (11.2) 59.7 (10.4) 58.6 (9.9) 59.8 (9.6) 82 (51.6) 160 (50.5) 85 (53.1) 175 (55.0) NR NR NR 8.1 (0.7) 8.1 (0.8) 8.1 (0.8) 8.1 (0.8) 141 (88.7) 269 (84.9) 136 (85.0) 277 (87.1) 13 (8.2) 34 (10.7) 19 (11.9) 36 (11.3) 3 (1.9) 5 (1.6) 3 (1.9) 4 (1.3) 2 (1.2) 9 (2.8) 2 (1.3) 1 (0.3) SOTA-EMPA 2021 Nov 27, 2017 to May 16, 2019 NR Placebo Sotagliflozin 400 mg Empagliflozin 25 mg 26 weeks 154 307 309 147 293 292 59.8 (9.6) 58.9 (9.7) 59.7 (9.6) 97 (51.3) 166 (54.1) 151 (48.9) NR NR NR 8.2 (0.8) 8.2 (0.9) 8.2 (0.9) 137 (89.0) 256 (83.4) 257 (83.2) 5 (3.2) 13 (4.2) 13 (4.2) 4 (2.6) 17 (5.5) 11 (3.6) 8 (5.2) 21 (6.9) 28 (9.0) SOTA-INS 2021 Sept 15, 2017 to Sept 17, 2019 2 weeks Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg 52 weeks 144 141 286 129 130 249 62.2 (8.9) 62.1 (10.2) 62.7 (9.1) 86 (59.7) 76 (53.9) 154 (53.8) NR NR NR 8.8 (0.8) 8.8 (0.8) 8.7 (0.8) 117 (81.3) 124 (87.9) 234 (81.8) 10 (6.9) 10 (7.1) 27 (9.4) 9 (6.3) 1 (0.7) 6 (2.1) 8 (5.5) 6 (4.3) 19 (6.6) Cherney DZI 2021 Aug 16, 2017 to Dec 11, 2019 4 weeks Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg 56.3 weeks 93 92 92 75 78 78 68.0 (8.3) 66.8 (10.0) 67.3 (9.6) 44 (47.8) 49 (53.3) 35 (48.7) NR 31.7 (5.7) 30.9 (5.4) 32.1 (6.2) 8.7 (3.2) 8.8 (3.3) 8.2 (2.6) 8.4 (1.1) 8.3 (1.0) 8.3 (0.9) 76 (81.7) 73 (79.3) 78 (84.8) 6 (6.5) 7 (7.6) 3 (3.3) 1 (1.1) 2 (2.2) 2 (2.2) 51 (58.4) 43 (46.8) 42 (45.7) Wada T 2022 Feb 15, 2018 to Jan 21, 2021 104 weeks Canagliflozin 100mg Placebo 15.4 (8.6) 16.5 (9.0) 154 154 124 127 62.5 (10.5) 62.4 (11.1) 115 (74.7) 129 (83.8) NR 26.7 (4.4) 27.1 (4.5) NR 7.8 (1.1) 7.8 (1.1) 0 0 154 (100) 154 (100 0 Takeshita Y 2022 Mar 2016 to Dec 2019 48 weeks Tofogliflozin 20mg Glimepiride 0.8mg NR 20 20 20 20 59.0 (16.1) 50.5 (19.8) 7 (35,0) 14 (70.0) 79.3 (18.2) 84.7 (25.4) 31.0 (6.7) 32.0 (8.8) 8.0 (2.3) 7.8 (2.0) 7.9 (1.1) 8.2 (2.2) 0 0 20 (100.0) 20 (100.0) 0 Cherney DZI 2023 Aug 16, 2017 to Oct 25, 2019 52 weeks Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg 17.7 (9.5) 17.2 (9.3) 16.3 (8.2) 260 263 264 224 240 232 69.3 (8.1) 69.6 (7.5) 69.5 (8.2) 149 (57.3) 143 (54.4) 152 (57.6) NR 32.5 (5.2) 32.3 (5.7) 32.4 (5.2) 9.2 (3.3) 9.1 (2.7) 9.0 (2.9) 8.3 (1.0) 8.3 (0.9) 8.3 (0.9) 220 (84.6) 231 (87.8) 215 (81.4) 12 (4.6) 14 (5.3) 15 (5.7) 5 (1.9) 7 (2.7) 8 (3.0) 23 (8.8) 11 (4.2) 26 (9.8) Herrington WG 2023 Jan 31, 2019 to Jul 2, 2024 162 weeks Placebo Empagliflozin 10 mg NR 3305 3304 2457 2549 63.8 (13.9) 63.9 (13.9) 2207 (66.8) 2210 (66.9) NR 29.8 (6.8) 29.7 (6.7) NR NR 1920 (58.1) 1939 (58.7) 134 (4.1) 128 (3.9) 1199 (36.3) 1194 (36.1) 52 (1.6) 43 (1.3) Shimoda M 2024 Apr 1, 2019 to Dec 31,2022 24 weeks Luseogliflozin 2.5mg Teneligliptin 20mg 10.1 (7.9) 9.2 (7.6) 49 54 44 52 60.8 (11.1) 62.6 (11.2) 26 (53.1) 31 (57.4) 69.9 (12.3) 71.9 (19.1) 27.0 (4.2) 27.2 (5.4) 8.3 (1.3) 8.2 (1.0) 7.6 (0.4) 7.5 (0.5) 0 0 49 (100.0) 54 (100.0) 0 GI neoplasm risk and SGLT2 inhibitors Control groups received either placebo or alternative antihyperglycemic agents, and pooled results revealed no significant elevation in GI neoplasm risk among SGLT2 inhibitor users compared with non-SGLT2 treatments (OR = 1.10, 95% CI 0.84–1.44; p = 0.46, Fig. 2 ). Site-specific outcomes Site-specific analyses revealed no statistically significant associations between SGLT2 inhibitor use and the risk of any individual GI neoplasms. The odds ratios with 95% confidence intervals were as follows: esophageal (OR = 1.12, 95% CI 0.37–3.45), gastric (1.20, 0.65–2.23), hepatic (0.62, 0.31–1.22), pancreatic (0.93, 0.52–1.66), colonic (1.28, 0.78–2.08), colorectal (0.76, 0.27–2.17), or rectal neoplasms (0.98, 0.49–1.97) (all p > 0.05; Supplementary eFigure 2). In all cases, the confidence intervals crossed the null value, indicating no consistent site-specific signal of increased or decreased risk. The point estimates and interval widths suggest that any true effect, if present, is likely to be small in magnitude. Drug-specific analyses Subgroup analyses by individual SGLT2 inhibitors identified no statistically significant association with gastrointestinal neoplasm risk for any agent. The odds ratios (95% CI) were as follows: canagliflozin, 1.02 (0.68–1.52); dapagliflozin, 1.29 (0.56–2.98); empagliflozin, 1.23 (0.70–2.19); ertugliflozin, 1.32 (0.39–4.46); tofogliflozin, 1.10 (0.32–3.72); and bexagliflozin, 0.85 (0.27–2.62) (all p > 0.05; eFigure 3). These findings suggest that none of the studied SGLT2 inhibitors confer a distinct advantage or harm with respect to GI neoplasm risk within the available trial data. Clinical subgroups Subgroup analyses were conducted according to baseline age, BMI, treatment duration, baseline HbA1c, and drug dosage. The pooled odds ratios with 95% confidence intervals across all these subgroups were consistently centered around the null value, with no consistent or clinically meaningful effect modification observed (Supplementary eFigures 4–10). Across prespecified subgroups (agent, dose, exposure duration, age, BMI, baseline HbA1c), pooled ORs clustered around unity, and interaction p -values were non-significant, indicating no reproducible effect modification (Fig. 3 ). In summary, no clearly identifiable high- or low-risk patient subgroup emerged from these analyses. Future studies with longer follow-up and a greater number of endpoint events will be required to detect potential subtle effect modifiers. Publication bias Egger’s test showed no evidence of publication bias (p = 0.15; t = 1.46). The funnel plot was largely symmetrical, indicating little evidence of publication bias (Supplementary eFigures 11–28). Discussion This comprehensive meta-analysis of 49 RCTs involving 49,054 patients with T2DM provides robust evidence that SGLT2 inhibitor therapy is not associated with an increased risk of gastrointestinal neoplasms (OR 1.10, 95% CI 0.84–1.44). The neutral signal was consistent across GI subsites, agents, and treatment durations. Dose-stratified analyses showed no association between SGLT2 inhibitors and GI neoplasms and no discernible dose–response within approved dosing ranges. Together, these results indicate that, at recommended doses used in contemporary trials, SGLT2 inhibitors were not associated with GI neoplasm risk, supporting the safety of currently recommended dosing with respect to GI neoplasm incidence. Subgroups were prespecified on biological and methodological grounds—BMI (adiposity-related inflammation); HbA1c (glycemic/hyperinsulinemic burden); exposure duration (latency; ≤52, 52–104, > 104 weeks); dose (FDA-labeled low vs high; potential dose–response); and agent (drug-specific selectivity or off-target effects). Across strata, pooled ORs centered on 1.0 with 95% CIs spanning unity, and interaction p-values were non-significant, indicating no reproducible effect modification. Mechanistically, SGLT2 inhibitors are proposed to engage several anticancer pathways, such as reducing hyperinsulinemia, attenuating systemic inflammation, and limiting glucose availability for tumors through urinary glucose excretion (68). Indeed, improvements in insulin sensitivity have been documented in meta-analyses, with more consistent effects observed for agents like dapagliflozin (69). Preclinical models further suggest that certain SGLT2 inhibitors may directly inhibit cancer cell glucose uptake (70). However, despite these plausible mechanisms, our synthesis of RCT data—under current clinical dosing and follow-up durations—did not show a measurable reduction in GI cancer incidence. This disconnect likely stems from several factors: (i) the drug concentrations required for direct antitumor effects in vitro often exceed plasma levels achieved with standard human dosing (71); (ii) the complex, multifactorial nature of human carcinogenesis—shaped by immune surveillance, the tumor microenvironment, and long-term adaptation—is not fully captured by animal or cell models (72); and (iii) the insufficient duration of RCTs, which may preclude the detection of slow, latency-dependent effects. Thus, while preclinical data outline plausible pathways, they have not translated into a clinically meaningful reduction in GI cancer risk, underscoring the need for longer, cancer-endpoint trials. The neutral findings from our RCT-based meta-analysis contrast with results from several large real-world observational studies suggesting lower risks for certain GI neoplasms with SGLT2 inhibitors. In a population-based study in Gastric Cancer, initiation of SGLT2 inhibitors was associated with a substantially reduced incidence of gastric cancer versus DPP-4 inhibitors (adjusted HR = 0.30) (13). A cohort from China’s Taiwan region likewise reported a lower overall cancer risk (HR 0.90, 95% CI 0.87–0.93), with favorable estimates for GI neoplasms (esophageal HR 0.57; colorectal/liver HR 0.90) (73). However, other real-world evidence—including quantitative overviews of reviews—has not shown a class-wide reduction in total or most site-specific cancers, and several population-based analyses report null associations after extensive adjustment. Taken together, observational results are heterogeneous: some signals suggest site-specific benefit, while others are neutral. Given the inherent limitations of nonrandomized designs (residual confounding by indication, immortal-time bias, differential screening, and unmeasured lifestyle factors), our RCT synthesis—though limited by relatively short follow-up—provides the highest internal validity and does not support a clinically meaningful reduction in GI cancer incidence within current trial durations. Longer RCTs with cancer endpoints, or rigorously specified target-trial emulations, are needed to verify or refute these real-world signals (74). From a safety perspective, our findings that GI neoplasms are not increased with SGLT2 inhibitor use further solidify the overall safety profile of this drug class. It is well-established that SGLT2 inhibitors are associated with an increased risk of genital mycotic infections, though these are typically manageable (75). Other risks, such as volume depletion and rare diabetic ketoacidosis events, are also recognized and can be mitigated with appropriate patient selection and monitoring (76, 77). Crucially, large outcome trials have consistently demonstrated significant cardiorenal benefits that, for most patients with T2DM, outweigh these known risks (78). Thus, our results provide reassurance that GI cancer risk does not appear to be a material safety concern for this class, supporting their continued use in clinical practice. To align our results with the current evidence base, we assessed concordance with two recent high-level syntheses. Xu et al. meta-analyzed 59 randomized controlled trials (n = 113,909) and found no significant effect of SGLT2 inhibitors on overall cancer (RR 1.01, 95% CI 0.94–1.08) or on gastrointestinal cancer (RR 1.02, 95% CI 0.85–1.22), consistent with our neutral primary results (79). Our analysis extends this evidence by focusing specifically on GI neoplasms with finer site granularity (esophageal, gastric, hepatic, pancreatic, colonic, colorectal, rectal, and biliary), incorporating more recent RCTs (through March 17, 2025), and reporting prespecified subgroup analyses (agent, FDA-labeled dose, exposure duration ≤ 52, 52–104, > 104 weeks, age, BMI, HbA1c) with interaction p-values, alongside sensitivity analyses and Egger’s tests. In a complementary overview of reviews, Pelletier et al. concluded that SGLT2 inhibitors as a class are not associated with increased risk of total or most site-specific neoplasms, while noting inconsistent drug-specific signals and substantial variability in methodological quality across reviews (80). Apparent differences from our findings likely reflect scope and design heterogeneity in that overview (e.g., pooled observational with randomized evidence, variable endpoint definitions, overlapping evidence bases, and differing follow-up windows), whereas our analysis is restricted to RCTs, harmonizes GI site definitions, and standardizes subgroup cut-points. Taken together, these syntheses corroborate our overall neutral conclusion for GI neoplasm risk and underscore the need for longer, cancer-endpoint RCTs to clarify any drug- or duration-dependent effects. This study has limitations. First, although randomization is intended to balance confounding, cancer was captured as a secondary outcome in most included RCTs; key baseline oncogenic risk factors (e.g., smoking, alcohol use, family history, prior screening) were variably measured and inconsistently reported across groups, leaving the possibility of residual confounding despite randomization. Second, the evaluation of long-term carcinogenicity is constrained by short follow-up: nearly half of the trials (47%) followed participants for ≤ 1 year, which may be insufficient to detect latency-dependent or cumulative exposure effects on GI neoplasms. Third, to maintain currency, we cite very recent studies (2024–2025); while this strengthens timeliness, some estimates may be based on immature follow-up and require confirmation with longer observation. These considerations temper the interpretation of the neutral findings and underscore the need for longer RCTs with prespecified cancer endpoints and standardized collection of baseline cancer risk factors. In conclusion, SGLT2 inhibitor treatment in adults with T2DM was not linked to an altered incidence of gastrointestinal neoplasms over the durations captured by the available trials, with consistent results across agents and anatomical subsites. The aggregate evidence supports intermediate-term oncologic safety and continued therapeutic use. Clarification of long-term risk should come from extended surveillance cohorts and dedicated cancer-endpoint studies. Abbreviations SGLT2 Sodium-glucose cotransporter 2 GLP-1 Glucagon-like peptide-1 DPP-4 Dipeptidyl peptidase-4 GI Gastrointestinal ORs Odds ratios RR Risk Ratio CIs Confidence intervals HR Hazard Ratio I² I-squared statistic SD Standard Deviation RoB 2 Risk of Bias 2 tool RCTs Randomized controlled trials T2DM Type 2 diabetes BMI Body mass index HbA1c Glycated hemoglobin CENTRAL Cochrane Central Register of Controlled Trials Declarations Ethics approval and consent to participate: Not applicable. Consent for publication: All the authors have provided their consent for publication of the manuscript. Availability of data and material: The authors confirm that the data supporting the findings of this study are available within the article and the supplementary material. Competing interests: The authors declare they have no conflict of interest. Funding: This work was supported by the Natural Science Foundation of China (grant numbers: 82300911, 32201056), Sichuan Province Science and Technology Program (application number: 2025ZNSFSC0741, 2025ZNSFSC1622), and Scientific Research Funding of Luzhou-Southwest Medical University (application number: 25YKDJCYJ0224). CRediT authorship contribution statement: Yu-Fan Zhang : investigation, software, data curation, writing-original draft, writing-review & editing; Jia-Jie Xie : data curation, methodology, software; Qi Wu : investigation, methodology; Xiao-Yu Zhou : methodology; Chen Zeng : software; Yan Zeng : validation; Yi-Meng He : software; Man Guo : conceptualization, resources, funding acquisition, supervision, writing-review & editing; Fang-Yuan Teng : funding acquisition, resources, writing-review & editing; Yong Xu : funding acquisition, supervision, resources, writing-review & editing. 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International journal of molecular sciences. 2022;23(7). Xu, B., Kang, B., Li, S., Chen, J., Zhou, J.. Association between sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis of randomized active-controlled trials. International journal of clinical pharmacy. 2025;47(5):1121-31. Pelletier, R., Ng, K., Alkabbani, W., Labib, Y., Mourad, N., Gamble, J.. The association of sodium-glucose cotransporter 2 inhibitors with cancer: An overview of quantitative systematic reviews. Endocrinology, diabetes & metabolism. 2020;3(3):e00145. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9272597","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":621447746,"identity":"13bcc7f3-5824-4eab-b3b3-20cc99c481f1","order_by":0,"name":"Yufan Zhang","email":"","orcid":"","institution":"Southwest Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yufan","middleName":"","lastName":"Zhang","suffix":""},{"id":621447747,"identity":"dbba0088-1b96-44bb-add5-c2b7be29a2dc","order_by":1,"name":"Jiajie Xie","email":"","orcid":"","institution":"Southwest Medical 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University","correspondingAuthor":true,"prefix":"","firstName":"Yong","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2026-03-31 00:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9272597/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9272597/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106869267,"identity":"54216f92-c80f-4308-95a4-814dd6fe8a9b","added_by":"auto","created_at":"2026-04-14 09:37:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":270613,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA Flow Diagram.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9272597/v1/5462b8e88d74fe968d4c58e2.png"},{"id":106869270,"identity":"d3675e90-3df4-480d-94f3-0cb3c0d687e0","added_by":"auto","created_at":"2026-04-14 09:37:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":244343,"visible":true,"origin":"","legend":"\u003cp\u003eRisks of GI neoplasms in patients with SGLT2 inhibitors treating for T2DM.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9272597/v1/3ac52e6221bafea445549626.png"},{"id":106869268,"identity":"8723c6dd-6c3b-4abb-8fba-da219b683883","added_by":"auto","created_at":"2026-04-14 09:37:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":347540,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analyses of gastrointestinal neoplasm risk with interaction \u003cem\u003ep\u003c/em\u003e-values\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9272597/v1/9c08a9819bcced1d4f1acf0f.png"},{"id":106869293,"identity":"b327c745-27ee-4880-a323-b74195a0db6c","added_by":"auto","created_at":"2026-04-14 09:38:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2932507,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9272597/v1/ae152c69-95d1-4904-b650-55e5c0694b19.pdf"},{"id":106869269,"identity":"4e7078d8-9ca1-43eb-8cbc-a3ded8fd46dd","added_by":"auto","created_at":"2026-04-14 09:37:48","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":97762038,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials20260114.docx","url":"https://assets-eu.researchsquare.com/files/rs-9272597/v1/5a55d228fc24974272186884.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sodium-Glucose Cotransporter-2 Inhibitors and Gastrointestinal Neoplasm Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe global prevalence of diabetes continues to escalate, affecting an estimated 589\u0026nbsp;million individuals in 2024, with projections reaching 853\u0026nbsp;million by 2050 (1). Poor glycemic control worsens vascular complications and is increasingly implicated in cancer pathogenesis (2, 3). Type 2 diabetes mellitus (T2DM) increases overall cancer risk by 10\u0026ndash;20%, particularly for liver, pancreatic, and colorectal neoplasms, via mechanisms like hyperinsulinemia, insulin resistance, and chronic inflammation (4).\u003c/p\u003e \u003cp\u003eThe long-term oncogenic implications of antihyperglycemic therapies remain controversial. Observational studies reveal divergent effects: insulin analogs and sulfonylureas may elevate gastrointestinal (GI) neoplasm risk (5), whereas metformin appears protective. In contrast, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists show neutral or inconsistent associations (6, 7). Sodium\u0026ndash;glucose cotransporter 2 (SGLT2) inhibitors\u0026mdash;now a cornerstone for cardiorenal protection in T2DM \u003csup\u003e(8)\u003c/sup\u003e\u0026mdash;lower glucose via insulin-independent blockade of renal glucose reabsorption, yet their potential carcinogenicity, particularly for GI neoplasms, remains uncertain. Randomized controlled trials (RCTs) provide discordant signals: EMPA-REG OUTCOME reported numerically fewer colorectal cancers with empagliflozin, whereas the CANVAS Program observed more colorectal and pancreatic events with canagliflozin; both findings were statistically non-significant (9, 10). Beyond these largely non-significant estimates, several large outcome trials have demonstrated statistically significant cardiorenal benefits with SGLT2 inhibitors (e.g., reduced heart-failure hospitalization and slower chronic kidney disease progression), prompting guideline-level uptake and sharpening the need to clarify long-term oncologic safety under real-world exposure. Program-level safety summaries have also noted site-specific, sometimes nominally significant, imbalances (e.g., colorectal/pancreatic events in canagliflozin programs; fewer colorectal events with empagliflozin (11)) that have not been consistent across agents or replicated across programs (12). Moreover, real-world cohorts have reported statistically significant associations\u0026mdash;for example, a lower gastric cancer incidence versus DPP-4 inhibitors (adjusted HR\u0026thinsp;\u0026asymp;\u0026thinsp;0.30) and reduced risks across several GI sites\u0026mdash;that contrast with neutral RCT results (13). Collectively, these mixed signals underscore both the clinical relevance and evidentiary uncertainty motivating our trial-based meta-analysis of GI neoplasms across agents, doses, and exposure windows.\u003c/p\u003e \u003cp\u003eThe relationship between SGLT2 inhibitor use and gastrointestinal neoplasm risk in T2DM remains inadequately defined, especially regarding dose\u0026ndash;response, treatment duration, and effect modification by patient characteristics. To address this gap, we conducted the first systematic meta-analysis to comprehensively evaluate the association between SGLT2 inhibitor therapy and GI neoplasms incidence, including esophageal, gastric, pancreatic, hepatic, colonic, colorectal, rectal, and biliary tract neoplasms. Furthermore, stratified subgroup analyses were performed to explore potential confounding effects of key variables, including treatment dosage, duration, mean age, and body mass index (BMI). Through this quantitative synthesis, our study aims to elucidate the safety profile of SGLT2 inhibitors in clinical practice and provide robust evidence to guide therapeutic decision-making.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe protocol for this systematic review and meta-analysis was registered with PROSPERO (CRD42024619019). The review followed the PRISMA 2020 reporting guidelines (14), ensuring methodological transparency and adherence to contemporary standards for evidence synthesis. The completed PRISMA 2020 checklist is available in Supplementary Appendix 1.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSearch Strategy\u003c/h2\u003e \u003cp\u003eWe systematically searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus for randomized controlled trials (RCTs) of SGLT2 inhibitors in people with type 2 diabetes from database inception to March 17, 2025. Additionally, we searched for unpublished and ongoing trials in ClinicalTrials.gov, manually reviewed the reference lists of relevant systematic reviews and meta-analyses, and examined grey literature available in clinical trial registries, without language restrictions. Following initial identification, we performed full-text screening of all records that covered SGLT2 inhibitors and/or GI neoplasms and included relevant studies in this section at the appropriate point.\u003c/p\u003e \u003cp\u003eThe search encompassed all SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) compared to placebo or active glucose-lowering agents (e.g., metformin, insulin) to assess GI neoplasms incidence during follow-up. The search strategy combined terms for SGLT2 inhibitors (e.g., *sodium-glucose cotransporter 2 inhibitor*, canagliflozin) and GI neoplasms (e.g., colorectal neoplasms, hepatocellular carcinoma), with full syntax provided in Supplementary Appendix 2.\u003c/p\u003e \u003cp\u003eTwo investigators independently screened titles/abstracts and assessed full texts for eligibility, with discrepancies resolved by consensus or a third reviewer. To minimize publication bias, search terms were not restricted to specific cancer-related vocabulary. Full texts and supplementary materials were comprehensively reviewed to identify unreported outcomes.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Selection\u003c/h3\u003e\n\u003cp\u003eStudies that fulfill the following criteria were encompassed in this meta-analysis: (1) participants were T2DM patients; (2) follow-up period\u0026thinsp;\u0026ge;\u0026thinsp;24 weeks; (3) the experimental group was provided SGLT2 inhibitor therapy (monotherapy or combination regimens), and the control group received placebo or non-SGLT2 glucose-lowering therapies; (4) reported GI neoplasms outcomes in publications or trial registries (e.g., ClinicalTrials.gov). Exclusion criteria: (1) non-RCTs, including reviews, case-control studies, cross-sectional studies, and case reports; (2) patients with type 1 diabetes mellitus or non-diabetic individuals; (3) non-English publications; (4) duplicate reports (Supplementary Appendix 3). For studies with multiple publications, the version with the longest follow-up or most complete data was selected. Two investigators independently screened eligible studies, with discrepancies resolved through consensus or consultation with a third reviewer.\u003c/p\u003e\n\u003ch3\u003eData Extraction and Quality Assessment\u003c/h3\u003e\n\u003cp\u003eData were extracted independently by two researchers and reviewed by a third researcher. The extracted data comprised: (1) study characteristics, such as author, region, year of publication, and treatment duration; (2) participant characteristics, including age, sex, sample size, diabetes duration, body mass index, hemoglobin A1c (HbA1c) and fasting blood glucose concentrations; (3) total number of GI neoplasms; (4) drug name and dose utilized by the experimental and control groups (Supplementary Appendix 4 for details). For the incidence of GI neoplasms, the total number of participants in both the experimental and control groups was estimated. If multiple publications from the same study population were identified, the report with the longest follow-up duration and most complete data was selected.\u003c/p\u003e \u003cp\u003eRCTs were assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. The evaluation criteria include review and judgment of \u0026ldquo;low risk,\u0026rdquo; \u0026ldquo;high risk,\u0026rdquo; or \u0026ldquo;unclear risk\u0026rdquo; in terms of sequence generation, allocation concealment, blinding, incomplete outcome data, as well as selective outcome reporting, and free of other bias (Supplementary eFigure 1). Yu-Fan Zhang independently assessed the risk of bias and compiled detailed descriptions of all studies.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using Stata 17.0 (StataCorp LLC). The odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to quantify associations. Heterogeneity was quantified with I\u0026sup2;. When I\u0026sup2; \u0026lt; 50%, fixed-effects models were applied; otherwise, random-effects models were used. Two-sided \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicated statistical significance; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.10 was considered suggestive in prespecified subgroup analyses.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSubgroup definitions\u003c/h3\u003e\n\u003cp\u003ePrespecified subgroups and their cut points were chosen a priori on biological and methodological grounds. Exposure duration was categorized as \u0026le;\u0026thinsp;52, 52\u0026ndash;104, and \u0026gt;\u0026thinsp;104 weeks, consistent with prior SGLT2 meta-analyses evaluating malignancy risk and intended to approximate short-, intermediate-, and extended exposure windows relevant to oncologic latency (15). Glycemic control was stratified by baseline HbA1c\u0026thinsp;\u0026le;\u0026thinsp;8.0% vs\u0026thinsp;\u0026gt;\u0026thinsp;8.0%, consistent with the 2024 ADA Standards of Care, which endorse less stringent glycemic goals (\u0026lt;\u0026thinsp;8.0%) for many adults and that are widely used to demarcate poorer control in trials (16). Adiposity followed established adult BMI categories (overweight: 25\u0026thinsp;\u0026le;\u0026thinsp;BMI\u0026thinsp;\u0026lt;\u0026thinsp;30 kg/m\u0026sup2;; obesity: BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2;) (17, 18). Dose was classified as FDA-labeled low (starting) vs high (maximum approved) for each agent (e.g., empagliflozin 10/25 mg; dapagliflozin 5/10 mg; canagliflozin 100/300 mg; ertugliflozin 5/15 mg); for agents approved outside the U.S., we used the corresponding national labels (e.g., tofogliflozin 20 mg; luseogliflozin 2.5\u0026ndash;5 mg).\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eEligible Studies and Characteristics\u003c/h2\u003e \u003cp\u003eA total of 2,791 citations were initially identified, and 356 full-text articles were assessed for eligibility. Based on the search strategy, 49 RCTs (19\u0026ndash;67) encompassing 41 articles involving 49,054 participants met the eligibility criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Of these, 28,651 participants were randomized to intervention groups receiving SGLT2 inhibitors, including ertugliflozin, bexagliflozin, dapagliflozin, empagliflozin, canagliflozin, tofogliflozin, and luseogliflozin. The included trials spanned multiple countries, with sample sizes ranging from 138 to 6,609 participants. Intervention durations varied between 24 weeks and 338 weeks. The mean baseline age of participants was 60.20 years (standard deviation [SD] 8.70), with 64.1% male. At baseline, the mean BMI was 30.80 kg/m\u0026sup2; (SD 5.80) and HbA1c was 8.17% (SD 0.97). Detailed participant characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Methodological quality assessment of the included studies, including descriptions of randomization and double-blinding procedures, is provided in Supplementary Appendix 5. The majority of studies demonstrated robust methodological rigor, with clear reporting of trial protocols.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of randomized controlled clinical trials and participants included.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"17\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInclusion Period\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFollow up\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRandomised treatments\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDuration of diabetes. (Mean. SD). years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTotal cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCompleted cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAge (mean. SD). years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo. (%) of male\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eWeight (mean. SD). kg\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBMI (mean. SD). kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eFPG (mmol/l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eHbA1c (mean. SD). %\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNo. (%) of White\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNo. (%) of Black or African American\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\"\u003e \u003cp\u003eNo. (%) of Asian\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c17\"\u003e \u003cp\u003eNo. (%) of Others\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStrojek K 2011\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eApr 2008 to Nov 2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eDapagliflozin 2.5mg Dapagliflozin 5mg Dapagliflozin 10mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.4 (5.7) \u003c/p\u003e \u003cp\u003e7.7 (6.0)\u003c/p\u003e \u003cp\u003e7.4 (5.7) \u003c/p\u003e \u003cp\u003e7.2 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e145 \u003c/p\u003e \u003cp\u003e154 \u003c/p\u003e \u003cp\u003e142\u003c/p\u003e \u003cp\u003e151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e133\u003c/p\u003e \u003cp\u003e140\u003c/p\u003e \u003cp\u003e132\u003c/p\u003e \u003cp\u003e141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60.3 (10.2)\u003c/p\u003e \u003cp\u003e59.9 (10.1)\u003c/p\u003e \u003cp\u003e60.2 (9.7)\u003c/p\u003e \u003cp\u003e58.9 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e71 (49.0) \u003c/p\u003e \u003cp\u003e77 (50.0) \u003c/p\u003e \u003cp\u003e71 (50.0) \u003c/p\u003e \u003cp\u003e66 (43.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e29.7 (4.6)\u003c/p\u003e \u003cp\u003e30.0 (5.1)\u003c/p\u003e \u003cp\u003e29.8 (5.2)\u003c/p\u003e \u003cp\u003e29.8 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e29.7 (4.6)\u003c/p\u003e \u003cp\u003e30.0 (5.1)\u003c/p\u003e \u003cp\u003e29.8 (5.2)\u003c/p\u003e \u003cp\u003e29.8 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.6 (2.1)\u003c/p\u003e \u003cp\u003e9.6 (2.1) \u003c/p\u003e \u003cp\u003e9.7 (2.1) \u003c/p\u003e \u003cp\u003e9.6 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.2 (0.7) \u003c/p\u003e \u003cp\u003e8.1 (0.8) \u003c/p\u003e \u003cp\u003e8.1 (0.8) \u003c/p\u003e \u003cp\u003e8.1 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e101\u003c/p\u003e \u003cp\u003e108\u003c/p\u003e \u003cp\u003e96\u003c/p\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e45\u003c/p\u003e \u003cp\u003e46\u003c/p\u003e \u003cp\u003e46\u003c/p\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNCT01095653 2012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMar 26, 2010 to March 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eDapagliflozin 5 mg \u003c/p\u003e \u003cp\u003eDapagliflozin 10 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e132\u003c/p\u003e \u003cp\u003e128\u003c/p\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e113\u003c/p\u003e \u003cp\u003e113\u003c/p\u003e \u003cp\u003e117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e49.9 (10.9)\u003c/p\u003e \u003cp\u003e53.0 (11.1)\u003c/p\u003e \u003cp\u003e51.2 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e87 (65.9)\u003c/p\u003e \u003cp\u003e84 (65.6)\u003c/p\u003e \u003cp\u003e86 (64.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e72.2 (13.2)\u003c/p\u003e \u003cp\u003e68.9 (11.4)\u003c/p\u003e \u003cp\u003e70.9 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e25.9 (3.6)\u003c/p\u003e \u003cp\u003e25.2 (3.3)\u003c/p\u003e \u003cp\u003e25.8 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e132 (100.0)\u003c/p\u003e \u003cp\u003e128 (100.0)\u003c/p\u003e \u003cp\u003e133 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLavalle-Gonz\u0026aacute;lez FJ 2013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eApr 2010 to Aug 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eSitagliptin 100 mg\u003c/p\u003e \u003cp\u003eCanagliflozin 100 mg\u003c/p\u003e \u003cp\u003eCanagliflozin 300mg.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.8 (5.3) \u003c/p\u003e \u003cp\u003e6.8 (5.2) \u003c/p\u003e \u003cp\u003e6.7 (5.4) \u003c/p\u003e \u003cp\u003e7.1 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e183 \u003c/p\u003e \u003cp\u003e366\u003c/p\u003e \u003cp\u003e368 \u003c/p\u003e \u003cp\u003e367\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e155 \u003c/p\u003e \u003cp\u003e319\u003c/p\u003e \u003cp\u003e322 \u003c/p\u003e \u003cp\u003e323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55.3 (9.8) \u003c/p\u003e \u003cp\u003e55.5 (9.6)\u003c/p\u003e \u003cp\u003e55.5 (9.4)\u003c/p\u003e \u003cp\u003e55.3 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e94 (51.4)\u003c/p\u003e \u003cp\u003e 172 (47.0) \u003c/p\u003e \u003cp\u003e174 (47.3) \u003c/p\u003e \u003cp\u003e165 (45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e86.6 (22.4)\u003c/p\u003e \u003cp\u003e87.7 (21.6) \u003c/p\u003e \u003cp\u003e88.8 (22.2) \u003c/p\u003e \u003cp\u003e85.4 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.1 (6.1)\u003c/p\u003e \u003cp\u003e32.0 (6.1)\u003c/p\u003e \u003cp\u003e32.4 (6.4) \u003c/p\u003e \u003cp\u003e31.4 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.1 (2.1) \u003c/p\u003e \u003cp\u003e9.4 (2.3)\u003c/p\u003e \u003cp\u003e9.3 (2.3) \u003c/p\u003e \u003cp\u003e9.6 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.0 (0.9)\u003c/p\u003e \u003cp\u003e7.9 (0.9)\u003c/p\u003e \u003cp\u003e7.9 (0.9\u003c/p\u003e \u003cp\u003e7.9 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e129 (70.5) \u003c/p\u003e \u003cp\u003e264 (72.1) \u003c/p\u003e \u003cp\u003e252 (68.5) \u003c/p\u003e \u003cp\u003e256 (69.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e3 (1.6) \u003c/p\u003e \u003cp\u003e13 (3.6) \u003c/p\u003e \u003cp\u003e16 (4.3) \u003c/p\u003e \u003cp\u003e13 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e30 (16.4) \u003c/p\u003e \u003cp\u003e41 (11.2)\u003c/p\u003e \u003cp\u003e51 (13.9) \u003c/p\u003e \u003cp\u003e60 (16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e21 (11.5) \u003c/p\u003e \u003cp\u003e48 (13.1) \u003c/p\u003e \u003cp\u003e49 (13.3) \u003c/p\u003e \u003cp\u003e38 (10.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBarnett AH 2014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSept 3, 2010. and Jul 26, 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eEmpagliflozin 10 mg\u003c/p\u003e \u003cp\u003eEmpagliflozin 25 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e319\u003c/p\u003e \u003cp\u003e98 \u003c/p\u003e \u003cp\u003e321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e278 \u003c/p\u003e \u003cp\u003e88 \u003c/p\u003e \u003cp\u003e280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e64.1 (8.7) \u003c/p\u003e \u003cp\u003e63.2 (8.5) \u003c/p\u003e \u003cp\u003e63.9 (9.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e181 (56.7)\u003c/p\u003e \u003cp\u003e60 (61.2) \u003c/p\u003e \u003cp\u003e189 (58.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e83.4 (19.0)\u003c/p\u003e \u003cp\u003e92.1 (21.4)\u003c/p\u003e \u003cp\u003e84.1 (20.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e30.6 (5.5)\u003c/p\u003e \u003cp\u003e 32.4 (5.4)\u003c/p\u003e \u003cp\u003e30.4 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.0 (2.7)\u003c/p\u003e \u003cp\u003e8.1 (1.9)\u003c/p\u003e \u003cp\u003e8.1 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.1 (0.8)\u003c/p\u003e \u003cp\u003e8.0 (0.8)\u003c/p\u003e \u003cp\u003e8.0 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e191 (59.9)\u003c/p\u003e \u003cp\u003e 69 (70.4)\u003c/p\u003e \u003cp\u003e185 (57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e6 (1.9)\u003c/p\u003e \u003cp\u003e3 (3.1)\u003c/p\u003e \u003cp\u003e13 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e119 (37.3)\u003c/p\u003e \u003cp\u003e 25 (25.5)\u003c/p\u003e \u003cp\u003e122 (38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e3 (0.9)\u003c/p\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKaku K 2014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOct 30, 2010 and Feb 28, 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eTofogliflozin 10mg\u003c/p\u003e \u003cp\u003eTofogliflozin 20mg\u003c/p\u003e \u003cp\u003eTofogliflozin 40mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.0 (6.1) \u003c/p\u003e \u003cp\u003e6.3 (7.1) \u003c/p\u003e \u003cp\u003e6.4 (5.1) \u003c/p\u003e \u003cp\u003e6.7 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56\u003c/p\u003e \u003cp\u003e57 \u003c/p\u003e \u003cp\u003e58 \u003c/p\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e48\u003c/p\u003e \u003cp\u003e54\u003c/p\u003e \u003cp\u003e56\u003c/p\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56.8 (9.9)\u003c/p\u003e \u003cp\u003e58.6 (9.8) \u003c/p\u003e \u003cp\u003e56.6 (10.2)\u003c/p\u003e \u003cp\u003e57.0 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e37 (66.1) \u003c/p\u003e \u003cp\u003e38 (66.7) \u003c/p\u003e \u003cp\u003e39 (67.2) \u003c/p\u003e \u003cp\u003e39 (67.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e71.2 (12.6) \u003c/p\u003e \u003cp\u003e67.3 (12.7) \u003c/p\u003e \u003cp\u003e68.1 (15.8) \u003c/p\u003e \u003cp\u003e68.7 (11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e26.0 (4.1) \u003c/p\u003e \u003cp\u003e25.1 (3.5) \u003c/p\u003e \u003cp\u003e25.0 (4.6) \u003c/p\u003e \u003cp\u003e25.8 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.4 (1.4) \u003c/p\u003e \u003cp\u003e9.5 (1.8) \u003c/p\u003e \u003cp\u003e9.4 (1.6) \u003c/p\u003e \u003cp\u003e9.3 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.4 (0.8) \u003c/p\u003e \u003cp\u003e8.5 (0.8) \u003c/p\u003e \u003cp\u003e8.3 (0.8) \u003c/p\u003e \u003cp\u003e8.3 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeiter LA 2014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMar 15, 2010 to May 30, 2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eDapagliflozin 10 mg QD.PO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.0 (8.4) \u003c/p\u003e \u003cp\u003e13.5 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e480\u003c/p\u003e \u003cp\u003e482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e441 \u003c/p\u003e \u003cp\u003e428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e63.6 (7.0) \u003c/p\u003e \u003cp\u003e63.9 (7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e323 (67.0)\u003c/p\u003e \u003cp\u003e321 (66.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e93.2 (16.8) \u003c/p\u003e \u003cp\u003e94.5 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e32.7 (5.7) \u003c/p\u003e \u003cp\u003e33.0 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.2 (2.5)\u003c/p\u003e \u003cp\u003e9.0 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.1 (0.8) \u003c/p\u003e \u003cp\u003e8.0 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e454 (94.6) \u003c/p\u003e \u003cp\u003e449 (93.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e9 (1.9) \u003c/p\u003e \u003cp\u003e10 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e6 (1.3) \u003c/p\u003e \u003cp\u003e7 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e11 (2.3)\u003c/p\u003e \u003cp\u003e16 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eJi L 2014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJun 2010 to Mar 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eDapagliflozin5mg\u003c/p\u003e \u003cp\u003eDapagliflozin10mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.3 (2.0)\u003c/p\u003e \u003cp\u003e1.2 (2.3) \u003c/p\u003e \u003cp\u003e1.7 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e132 \u003c/p\u003e \u003cp\u003e128 \u003c/p\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e113 \u003c/p\u003e \u003cp\u003e113 \u003c/p\u003e \u003cp\u003e117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e49.9 (10.9) 53.0 (11.1)\u003c/p\u003e \u003cp\u003e51.2 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e87 (65.9) \u003c/p\u003e \u003cp\u003e84 (65.6) \u003c/p\u003e \u003cp\u003e86 (64.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e72.2 (13.2) 68.9 (11.4) \u003c/p\u003e \u003cp\u003e70.9 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e25.9 (3.6) \u003c/p\u003e \u003cp\u003e25.2 (3.3) \u003c/p\u003e \u003cp\u003e25.8 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.3 (2.4) \u003c/p\u003e \u003cp\u003e8.6 (1.8) \u003c/p\u003e \u003cp\u003e9.0 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.4 (1.0) \u003c/p\u003e \u003cp\u003e8.1 (0.7) \u003c/p\u003e \u003cp\u003e8.3 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e132 \u003c/p\u003e \u003cp\u003e128 \u003c/p\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRosenstock J 2014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMar 2011 to Apr 2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eEmpagliflozin 10 mg \u003c/p\u003e \u003cp\u003eEmpagliflozin 25 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e189 \u003c/p\u003e \u003cp\u003e187 \u003c/p\u003e \u003cp\u003e190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e161 \u003c/p\u003e \u003cp\u003e159 \u003c/p\u003e \u003cp\u003e168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55.3 (10.1) 56.7 (8.7)\u003c/p\u003e \u003cp\u003e58.0 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e75 (39.9)\u003c/p\u003e \u003cp\u003e97 (52.2)\u003c/p\u003e \u003cp\u003e84 (44.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e95.5 (17.5)\u003c/p\u003e \u003cp\u003e96.7 (17.9)\u003c/p\u003e \u003cp\u003e95.9 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e34.7 (4.3)\u003c/p\u003e \u003cp\u003e34.7 (3.8) \u003c/p\u003e \u003cp\u003e35.0 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.4 (2.5)\u003c/p\u003e \u003cp\u003e8.8 (2.7) \u003c/p\u003e \u003cp\u003e8.3 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.3 (0.1)\u003c/p\u003e \u003cp\u003e8.4 (0.1)\u003c/p\u003e \u003cp\u003e8.3 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e174 (93) \u003c/p\u003e \u003cp\u003e175 (94) \u003c/p\u003e \u003cp\u003e182 (96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e8 (4) \u003c/p\u003e \u003cp\u003e7 (4) \u003c/p\u003e \u003cp\u003e4 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e6 (3) \u003c/p\u003e \u003cp\u003e4 (2) \u003c/p\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNauck MA 2014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMar 31, 2008 to Dec 15, 2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDapagliflozin (2.5. 5. or 10 mg)\u003c/p\u003e \u003cp\u003eGlipizide (5. 10. or 20 mg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e406\u003c/p\u003e \u003cp\u003e408\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e322\u003c/p\u003e \u003cp\u003e314\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.1 (9.4) \u003c/p\u003e \u003cp\u003e58.6 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e221 (55.3)\u003c/p\u003e \u003cp\u003e220 (54.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.7 (5.1)\u003c/p\u003e \u003cp\u003e31.2 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.0 (2.1)\u003c/p\u003e \u003cp\u003e9.1 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.7 (0.9)\u003c/p\u003e \u003cp\u003e7.7 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e327 (81.8)\u003c/p\u003e \u003cp\u003e323 (80.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e26 (6.5)\u003c/p\u003e \u003cp\u003e24 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e27 (6.8)\u003c/p\u003e \u003cp\u003e34 (8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e20 (5.0)\u003c/p\u003e \u003cp\u003e20 (5.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRidderstr\u0026aring;le M 2014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAug 2010 to Jun 2011.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEmpagliflozin 25mg\u003c/p\u003e \u003cp\u003eglimepiride 1\u0026ndash;4 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e769 \u003c/p\u003e \u003cp\u003e780\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e610 \u003c/p\u003e \u003cp\u003e589\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55.7 (10.4)\u003c/p\u003e \u003cp\u003e56.2 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e421 (54.0)\u003c/p\u003e \u003cp\u003e432 (56.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e83.0 (19.2) \u003c/p\u003e \u003cp\u003e82.5 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e30.3 (5.3) \u003c/p\u003e \u003cp\u003e30.0 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8\u0026middot;32 (1\u0026middot;98) \u003c/p\u003e \u003cp\u003e8\u0026middot;32 (1\u0026middot;77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.92 (0.86)\u003c/p\u003e \u003cp\u003e7.92 (0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e519 (66.5) \u003c/p\u003e \u003cp\u003e498 (65.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e8 (1.0)\u003c/p\u003e \u003cp\u003e 12 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e253 (32.4) \u003c/p\u003e \u003cp\u003e254 (33.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0 \u003c/p\u003e \u003cp\u003e1 (\u0026lt;\u0026thinsp;1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInagaki N 2014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJul 2011 to Aug 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eCanagliflozin 100 mg \u003c/p\u003e \u003cp\u003eCanagliflozin 200 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.6 (5.8) \u003c/p\u003e \u003cp\u003e4.7 (4.6) \u003c/p\u003e \u003cp\u003e5.9 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e93 \u003c/p\u003e \u003cp\u003e90 \u003c/p\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e74\u003c/p\u003e \u003cp\u003e84\u003c/p\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.2 (11.0) \u003c/p\u003e \u003cp\u003e58.4 (10.4) \u003c/p\u003e \u003cp\u003e57.4 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e60 (64.5) \u003c/p\u003e \u003cp\u003e59 (65.6) \u003c/p\u003e \u003cp\u003e72 (81.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e68.6 (15.2) 69.1 (14.5) \u003c/p\u003e \u003cp\u003e69.9 (14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e25.9 (4.4) \u003c/p\u003e \u003cp\u003e25.6 (4.2) \u003c/p\u003e \u003cp\u003e25.4 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.1 (1.8) \u003c/p\u003e \u003cp\u003e8.8 (2.0) \u003c/p\u003e \u003cp\u003e9.2 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.0 (0.7)\u003c/p\u003e \u003cp\u003e8.0 (0.7) \u003c/p\u003e \u003cp\u003e8.0 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e93 (100.0)\u003c/p\u003e \u003cp\u003e90 (100.0) \u003c/p\u003e \u003cp\u003e88 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWilding JP 2014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eApr 30, 2008 to May 19, 2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo Dapagliflozin2.5mg Dapagliflozin5/10mg Dapagliflozin10mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.5 (7.3) \u003c/p\u003e \u003cp\u003e13.6 (6.6) \u003c/p\u003e \u003cp\u003e13.1 (7.8) \u003c/p\u003e \u003cp\u003e14.2 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e193\u003c/p\u003e \u003cp\u003e202\u003c/p\u003e \u003cp\u003e211\u003c/p\u003e \u003cp\u003e194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e168\u003c/p\u003e \u003cp\u003e180\u003c/p\u003e \u003cp\u003e186\u003c/p\u003e \u003cp\u003e178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.8 (8.6) \u003c/p\u003e \u003cp\u003e59.8 (7.6) \u003c/p\u003e \u003cp\u003e59.3 (7.9) \u003c/p\u003e \u003cp\u003e59.3 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e98 (50.8) \u003c/p\u003e \u003cp\u003e102 (50.5) \u003c/p\u003e \u003cp\u003e111 (52.6) \u003c/p\u003e \u003cp\u003e107 (55.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e94.5 (19.8) \u003c/p\u003e \u003cp\u003e93.0 (16.7) \u003c/p\u003e \u003cp\u003e93.3 (17.4) \u003c/p\u003e \u003cp\u003e94.5 (16.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e33.1 (5.9) \u003c/p\u003e \u003cp\u003e33.0 (5.0) \u003c/p\u003e \u003cp\u003e33.0 (5.3) \u003c/p\u003e \u003cp\u003e33.4 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.5 (3.2) \u003c/p\u003e \u003cp\u003e10.0 (3.3) \u003c/p\u003e \u003cp\u003e10.3 (3.3) \u003c/p\u003e \u003cp\u003e9.6 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.5 (0.8)\u003c/p\u003e \u003cp\u003e8.5 (0.8) \u003c/p\u003e \u003cp\u003e8.6 (0.9) \u003c/p\u003e \u003cp\u003e8.6 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e186 (96.4)\u003c/p\u003e \u003cp\u003e190 (94.1) \u003c/p\u003e \u003cp\u003e200 (94.8) \u003c/p\u003e \u003cp\u003e184 (94.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e6 (3.1) \u003c/p\u003e \u003cp\u003e3 (1.5) \u003c/p\u003e \u003cp\u003e5 (2.4) \u003c/p\u003e \u003cp\u003e5 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e0 \u003c/p\u003e \u003cp\u003e7 (3.5) \u003c/p\u003e \u003cp\u003e3 (1.4) \u003c/p\u003e \u003cp\u003e3 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e1 (0.5) \u003c/p\u003e \u003cp\u003e2 (1.0) \u003c/p\u003e \u003cp\u003e3 (1.4) \u003c/p\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBailey CJ 2015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJun 7, 2010 to May 23, 2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eCanagliflozin 100 mg \u003c/p\u003e \u003cp\u003eCanagliflozin 300 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.4 (7.3)\u003c/p\u003e \u003cp\u003e12.3 (7.8)\u003c/p\u003e \u003cp\u003e11.3 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e237 \u003c/p\u003e \u003cp\u003e241 \u003c/p\u003e \u003cp\u003e236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e158 \u003c/p\u003e \u003cp\u003e184 \u003c/p\u003e \u003cp\u003e178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e63.2 (6.2)\u003c/p\u003e \u003cp\u003e64.3 (6.5)\u003c/p\u003e \u003cp\u003e63.4 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e143 (60.3) \u003c/p\u003e \u003cp\u003e124 (51.5) \u003c/p\u003e \u003cp\u003e129 (54.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e91.1 (17.5) \u003c/p\u003e \u003cp\u003e88.4 (15.6) \u003c/p\u003e \u003cp\u003e88.8 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.8 (4.8) \u003c/p\u003e \u003cp\u003e31.4 (4.4)\u003c/p\u003e \u003cp\u003e31.5 (4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.7 (2.2)\u003c/p\u003e \u003cp\u003e8.9 (2.2)\u003c/p\u003e \u003cp\u003e8.5 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.8 (0.8)\u003c/p\u003e \u003cp\u003e7.8 (0.8)\u003c/p\u003e \u003cp\u003e7.7 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e185 (78.1) \u003c/p\u003e \u003cp\u003e194 (80.5) \u003c/p\u003e \u003cp\u003e173 (73.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e20 (8.4) \u003c/p\u003e \u003cp\u003e18 (7.5) \u003c/p\u003e \u003cp\u003e19 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e21 (8.9) \u003c/p\u003e \u003cp\u003e15 (6.2) \u003c/p\u003e \u003cp\u003e25 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e11 (4.6) \u003c/p\u003e \u003cp\u003e14 (5.8) \u003c/p\u003e \u003cp\u003e19 (8.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eJ Rosenstock 2015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNov 2009 to May 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eEmpagliflozin 10\u0026thinsp;mg \u003c/p\u003e \u003cp\u003eEmpagliflozin 25\u0026thinsp;mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e170 \u003c/p\u003e \u003cp\u003e169 \u003c/p\u003e \u003cp\u003e155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e147 \u003c/p\u003e \u003cp\u003e153 \u003c/p\u003e \u003cp\u003e129\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.1 (9.4) \u003c/p\u003e \u003cp\u003e58.6 (9.8) \u003c/p\u003e \u003cp\u003e59.9 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e90 (53) \u003c/p\u003e \u003cp\u003e93 (55) \u003c/p\u003e \u003cp\u003e93 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e90.5 (1.7) \u003c/p\u003e \u003cp\u003e91.6 (1.5) \u003c/p\u003e \u003cp\u003e94.7 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.8 (6.0) \u003c/p\u003e \u003cp\u003e32.1 (5.8) \u003c/p\u003e \u003cp\u003e32.7 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e7.9 (0.2) \u003c/p\u003e \u003cp\u003e7.7 (0.2) 8.1\u0026thinsp;(0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.1\u0026thinsp;(0.1) \u003c/p\u003e \u003cp\u003e8.3 (0.1) 8.3 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e113 (66) \u003c/p\u003e \u003cp\u003e119 (70) \u003c/p\u003e \u003cp\u003e111 (72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e21 (12) \u003c/p\u003e \u003cp\u003e12 (7) \u003c/p\u003e \u003cp\u003e15 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e33 (19) \u003c/p\u003e \u003cp\u003e37 (22) \u003c/p\u003e \u003cp\u003e28 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e3 (2) \u003c/p\u003e \u003cp\u003e1 (1) \u003c/p\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRoden M 2015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFeb 2011 to May 2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eEmpagliflozin 10 mg\u003c/p\u003e \u003cp\u003eEmpagliflozin 25 mg\u003c/p\u003e \u003cp\u003eSitagliptin 100 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e228\u003c/p\u003e \u003cp\u003e224 \u003c/p\u003e \u003cp\u003e224\u003c/p\u003e \u003cp\u003e223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e119\u003c/p\u003e \u003cp\u003e147 \u003c/p\u003e \u003cp\u003e143\u003c/p\u003e \u003cp\u003e136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e54.9 (10.9)\u003c/p\u003e \u003cp\u003e56.2 (11.6)\u003c/p\u003e \u003cp\u003e53.8 (11.6)\u003c/p\u003e \u003cp\u003e55.1 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e123 (53.9) \u003c/p\u003e \u003cp\u003e142 (63.4) \u003c/p\u003e \u003cp\u003e145 (64.7) \u003c/p\u003e \u003cp\u003e141 (63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e78.2 (19.9)\u003c/p\u003e \u003cp\u003e78.4 (18.7) 77.8 (18.0) 79.3 (20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e28.7 (6.2) \u003c/p\u003e \u003cp\u003e28.3 (5.5)\u003c/p\u003e \u003cp\u003e28.2 (5.5)\u003c/p\u003e \u003cp\u003e28.2 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.6 (2.0)\u003c/p\u003e \u003cp\u003e8.5 (1.8)\u003c/p\u003e \u003cp\u003e8.5 (1.9) \u003c/p\u003e \u003cp\u003e8.2 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.9 (0.8) \u003c/p\u003e \u003cp\u003e7.9 (0.9) \u003c/p\u003e \u003cp\u003e7.9 (0.9) \u003c/p\u003e \u003cp\u003e7.9 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e76 (33.3) \u003c/p\u003e \u003cp\u003e77 (34.4) \u003c/p\u003e \u003cp\u003e73 (32.6) \u003c/p\u003e \u003cp\u003e76 (34.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e6 (2.6) \u003c/p\u003e \u003cp\u003e3 (1.3) \u003c/p\u003e \u003cp\u003e7 (3.1) \u003c/p\u003e \u003cp\u003e3 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e146 (64.0) \u003c/p\u003e \u003cp\u003e143 (63.8) \u003c/p\u003e \u003cp\u003e144 (64.3) \u003c/p\u003e \u003cp\u003e143 (64.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0 \u003c/p\u003e \u003cp\u003e1 (0.4) \u003c/p\u003e \u003cp\u003e0 \u003c/p\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRosenstock Julio 2015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJul 2012 to Jan 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSaxagliptin 5mg and Dapagliflozin 10mg plus MET \u003c/p\u003e \u003cp\u003eSaxagliptin 5mg and Placebo plus MET Dapagliflozin 10mg and Placebo plus MET\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.6 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e179\u003c/p\u003e \u003cp\u003e176\u003c/p\u003e \u003cp\u003e179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e161 \u003c/p\u003e \u003cp\u003e160 \u003c/p\u003e \u003cp\u003e169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e53 (10)\u003c/p\u003e \u003cp\u003e55 (10)\u003c/p\u003e \u003cp\u003e54 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e94 (53.4) \u003c/p\u003e \u003cp\u003e89 (49.7) \u003c/p\u003e \u003cp\u003e85 (47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e87.1 (18.0)\u003c/p\u003e \u003cp\u003e88.0 (18.7)\u003c/p\u003e \u003cp\u003e86.3 (18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.8 (4.8)\u003c/p\u003e \u003cp\u003e31.8 (5.1)\u003c/p\u003e \u003cp\u003e31.5 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e10 (2.53)\u003c/p\u003e \u003cp\u003e10.7 (2.5)\u003c/p\u003e \u003cp\u003e10.3 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.92 (1.18)\u003c/p\u003e \u003cp\u003e9.03 (1.05)\u003c/p\u003e \u003cp\u003e8.87 (1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e120 (67.0)\u003c/p\u003e \u003cp\u003e121 (68.7)\u003c/p\u003e \u003cp\u003e131 (73.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e22 (12.3)\u003c/p\u003e \u003cp\u003e22 (12.5)\u003c/p\u003e \u003cp\u003e16 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e12 (6.7)\u003c/p\u003e \u003cp\u003e11 (6.3)\u003c/p\u003e \u003cp\u003e10 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e25 (14.0)\u003c/p\u003e \u003cp\u003e22 (12.5)\u003c/p\u003e \u003cp\u003e22 (12.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRosenstock J 2016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMay 16, 2013 to Dec 1,2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMetformin XR \u003c/p\u003e \u003cp\u003eCanagliflozin 100 mg\u003c/p\u003e \u003cp\u003eCanagliflozin 300 mg \u003c/p\u003e \u003cp\u003eCanagliflozin 100 mg\u0026thinsp;+\u0026thinsp;Metformin XR\u003c/p\u003e \u003cp\u003eCanagliflozin 300 mg\u0026thinsp;+\u0026thinsp;Metformin XR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.3 (4.5)\u003c/p\u003e \u003cp\u003e3.5 (4.4)\u003c/p\u003e \u003cp\u003e3.3 (4.4)\u003c/p\u003e \u003cp\u003e2.9 (3.3)\u003c/p\u003e \u003cp\u003e3.3 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e237\u003c/p\u003e \u003cp\u003e237\u003c/p\u003e \u003cp\u003e238\u003c/p\u003e \u003cp\u003e237\u003c/p\u003e \u003cp\u003e237\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e205\u003c/p\u003e \u003cp\u003e211\u003c/p\u003e \u003cp\u003e216\u003c/p\u003e \u003cp\u003e225\u003c/p\u003e \u003cp\u003e212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55.2 (9.8)\u003c/p\u003e \u003cp\u003e54.0 (10.7)\u003c/p\u003e \u003cp\u003e55.8 (9.6)\u003c/p\u003e \u003cp\u003e54.2 (9.7)\u003c/p\u003e \u003cp\u003e55.4 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e116 (48.9)\u003c/p\u003e \u003cp\u003e105 (44.3)\u003c/p\u003e \u003cp\u003e125 (52.5)\u003c/p\u003e \u003cp\u003e108 (45.6)\u003c/p\u003e \u003cp\u003e115 (48.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e92.1 (20.1)\u003c/p\u003e \u003cp\u003e90.2 (18.6) 93.0 (19.9)\u003c/p\u003e \u003cp\u003e88.3 (17.6) 91.4 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e33.0 (6.0)\u003c/p\u003e \u003cp\u003e32.4 (5.4) \u003c/p\u003e \u003cp\u003e32.6 (5.8)\u003c/p\u003e \u003cp\u003e31.9 (5.3) \u003c/p\u003e \u003cp\u003e32.8 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e10.6 (2.7)\u003c/p\u003e \u003cp\u003e10.9 (3.0) \u003c/p\u003e \u003cp\u003e10.7 (2.9)\u003c/p\u003e \u003cp\u003e10.6 (2.8) \u003c/p\u003e \u003cp\u003e11.2 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.8 (1.2)\u003c/p\u003e \u003cp\u003e8.8 (1.2)\u003c/p\u003e \u003cp\u003e8.8 (1.2)\u003c/p\u003e \u003cp\u003e8.8 (1.1)\u003c/p\u003e \u003cp\u003e8.8 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e192 (81.0)\u003c/p\u003e \u003cp\u003e192 (81.0) \u003c/p\u003e \u003cp\u003e208 (87.4)\u003c/p\u003e \u003cp\u003e189 (79.7) \u003c/p\u003e \u003cp\u003e187 (78.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e9 (3.8)\u003c/p\u003e \u003cp\u003e12 (5.1)\u003c/p\u003e \u003cp\u003e8 (3.4) \u003c/p\u003e \u003cp\u003e6 (2.5) \u003c/p\u003e \u003cp\u003e8 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e9 (3.8)\u003c/p\u003e \u003cp\u003e4 (1.7) \u003c/p\u003e \u003cp\u003e4 (1.7)\u003c/p\u003e \u003cp\u003e6 (2.5) \u003c/p\u003e \u003cp\u003e5 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e27 (11.4)\u003c/p\u003e \u003cp\u003e29 (12.2) 18 (7.6)\u003c/p\u003e \u003cp\u003e36 (15.2) \u003c/p\u003e \u003cp\u003e37 (15.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHaneda M 2016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMay 2011 to October 2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eLuseogliflozin 2.5 or 5mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.6 (10.4) 10.4 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50\u003c/p\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e45\u003c/p\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e68.4 (8.9)\u003c/p\u003e \u003cp\u003e67.9 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e39 (78.0)\u003c/p\u003e \u003cp\u003e72 (75.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e67.8 (11.8) \u003c/p\u003e \u003cp\u003e66.9 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e25.8 (4.0) \u003c/p\u003e \u003cp\u003e25.5 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e7.9 (1.5) \u003c/p\u003e \u003cp\u003e7.8 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.7 (0.7) \u003c/p\u003e \u003cp\u003e7.7 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKadowaki T 2017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJan 2015 to Jan 2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u0026thinsp;+\u0026thinsp;Teneligliptin 20\u0026thinsp;mg\u003c/p\u003e \u003cp\u003eCanagliflozin 100\u0026thinsp;mg\u0026thinsp;+\u0026thinsp;Teneligliptin 20\u0026thinsp;mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.5 (3.9)\u003c/p\u003e \u003cp\u003e8.3 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68\u003c/p\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e61\u003c/p\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56.0 (9.5)\u003c/p\u003e \u003cp\u003e58.4 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e53 (77.9)\u003c/p\u003e \u003cp\u003e54 (77.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e73.3 (12.9)\u003c/p\u003e \u003cp\u003e71.3 (15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e26.4 (3.9)\u003c/p\u003e \u003cp\u003e25.5 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.2 (1.9)\u003c/p\u003e \u003cp\u003e9.7 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.9 (0.8)\u003c/p\u003e \u003cp\u003e8.2 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePratley RE 2017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eApr 22,2014 to\u003c/p\u003e \u003cp\u003eMay 26,2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eErtugliflozin 5 mg \u003c/p\u003e \u003cp\u003eErtugliflozin 15 mg\u003c/p\u003e \u003cp\u003eSitagliptin 100 mg Ertugliflozin 5 mg\u0026thinsp;+\u0026thinsp;Sitagliptin 100 mg Ertugliflozin 15 mg\u0026thinsp;+\u0026thinsp;Sitagliptin 100 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.1 (5.4) \u003c/p\u003e \u003cp\u003e7.3 (5.4)\u003c/p\u003e \u003cp\u003e6.2 (5.2) \u003c/p\u003e \u003cp\u003e7.0 (5.6) \u003c/p\u003e \u003cp\u003e6.9 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e250\u003c/p\u003e \u003cp\u003e248\u003c/p\u003e \u003cp\u003e247\u003c/p\u003e \u003cp\u003e243\u003c/p\u003e \u003cp\u003e245\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e226\u003c/p\u003e \u003cp\u003e217\u003c/p\u003e \u003cp\u003e219\u003c/p\u003e \u003cp\u003e221\u003c/p\u003e \u003cp\u003e218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55.1 (10.1) \u003c/p\u003e \u003cp\u003e55.3 (9.5) \u003c/p\u003e \u003cp\u003e54.8 (10.7) \u003c/p\u003e \u003cp\u003e55.2 (10.4) \u003c/p\u003e \u003cp\u003e55.1 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e127 (50.8) \u003c/p\u003e \u003cp\u003e134 (54.0) \u003c/p\u003e \u003cp\u003e154 (62.3) \u003c/p\u003e \u003cp\u003e123 (50.6) \u003c/p\u003e \u003cp\u003e126 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e88.6 (22.2) \u003c/p\u003e \u003cp\u003e88.0 (20.3) \u003c/p\u003e \u003cp\u003e89.8 (23.5) \u003c/p\u003e \u003cp\u003e89.5 (20.8) \u003c/p\u003e \u003cp\u003e87.5 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.8 (6.2) \u003c/p\u003e \u003cp\u003e31.5 (5.8) \u003c/p\u003e \u003cp\u003e31.7 (6.5) \u003c/p\u003e \u003cp\u003e32.5 (6.7) \u003c/p\u003e \u003cp\u003e31.8 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e10.23 (2.9) \u003c/p\u003e \u003cp\u003e9.97 (2.54) \u003c/p\u003e \u003cp\u003e9.69 (2.59)\u003c/p\u003e \u003cp\u003e10.21(2.46) \u003c/p\u003e \u003cp\u003e9.84 (2.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.6 (1.0) \u003c/p\u003e \u003cp\u003e8.6 (1.0) \u003c/p\u003e \u003cp\u003e8.5 (1.0) \u003c/p\u003e \u003cp\u003e8.6 (1.0) \u003c/p\u003e \u003cp\u003e8.6 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e7 (2.8) \u003c/p\u003e \u003cp\u003e4 (1.6) \u003c/p\u003e \u003cp\u003e4 (1.6) \u003c/p\u003e \u003cp\u003e2 (0.8) \u003c/p\u003e \u003cp\u003e4 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e7 (2.8) \u003c/p\u003e \u003cp\u003e6 (2.4) \u003c/p\u003e \u003cp\u003e11 (4.5) \u003c/p\u003e \u003cp\u003e12 (4.9) \u003c/p\u003e \u003cp\u003e10 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e22 (8.8) \u003c/p\u003e \u003cp\u003e22 (8.9) \u003c/p\u003e \u003cp\u003e29 (11.7) \u003c/p\u003e \u003cp\u003e22 (9.1) \u003c/p\u003e \u003cp\u003e36 (14.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e8 (3.2) \u003c/p\u003e \u003cp\u003e11 (4.4) \u003c/p\u003e \u003cp\u003e10 (3.6) \u003c/p\u003e \u003cp\u003e10 (4.1) \u003c/p\u003e \u003cp\u003e6 (2.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTerra SG 2017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOct 9, 2013 to Jul 28, 2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eErtugliflozin 5 mg \u003c/p\u003e \u003cp\u003eErtugliflozin 15 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.6 (4.5) \u003c/p\u003e \u003cp\u003e5.1 (5.1) \u003c/p\u003e \u003cp\u003e5.2 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e153\u003c/p\u003e \u003cp\u003e156 \u003c/p\u003e \u003cp\u003e152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e121\u003c/p\u003e \u003cp\u003e137 \u003c/p\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56.1 (10.9) \u003c/p\u003e \u003cp\u003e56.8 (11.4) \u003c/p\u003e \u003cp\u003e56.2 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e82 (53.6) \u003c/p\u003e \u003cp\u003e89 (57.1) \u003c/p\u003e \u003cp\u003e90 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e94.2 (25.2) \u003c/p\u003e \u003cp\u003e94.0 (25.4) \u003c/p\u003e \u003cp\u003e90.6 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e33.3 (6.8) \u003c/p\u003e \u003cp\u003e33.2 (7.4) \u003c/p\u003e \u003cp\u003e32.5 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e10.0 (2.5) \u003c/p\u003e \u003cp\u003e10.0 (2.7) \u003c/p\u003e \u003cp\u003e9.9 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.1 (0.9) \u003c/p\u003e \u003cp\u003e8.2 (0.9) \u003c/p\u003e \u003cp\u003e8.4 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e126 (82.4) \u003c/p\u003e \u003cp\u003e134 (85.9) \u003c/p\u003e \u003cp\u003e126 (82.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e9 (5.9)\u003c/p\u003e \u003cp\u003e10 (6.4) \u003c/p\u003e \u003cp\u003e10 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e15 (9.8) \u003c/p\u003e \u003cp\u003e10 (6.4) \u003c/p\u003e \u003cp\u003e14 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e3 (2.0)\u003c/p\u003e \u003cp\u003e2 (1.3)\u003c/p\u003e \u003cp\u003e2 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCANVAS-R 2018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJan 16, 2014 to Feb 23,2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e156 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eCanagliflozin 100 and 300 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2905 \u003c/p\u003e \u003cp\u003e2907\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2866\u003c/p\u003e \u003cp\u003e2872\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e64.0 (8.3) \u003c/p\u003e \u003cp\u003e63.9 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1794 (61.8)\u003c/p\u003e \u003cp\u003e1854 (63.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e2372 (81.7)\u003c/p\u003e \u003cp\u003e2393 (82.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e125 (4.3)\u003c/p\u003e \u003cp\u003e106 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e245 (8.4)\u003c/p\u003e \u003cp\u003e244 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e245 (5.7)\u003c/p\u003e \u003cp\u003e164 (5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCANVAS 2018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDec 9, 2009 to Feb 22, 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e338 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eCanagliflozin 100 mg \u003c/p\u003e \u003cp\u003eCanagliflozin 300 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1442 \u003c/p\u003e \u003cp\u003e1445\u003c/p\u003e \u003cp\u003e1443\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1297\u003c/p\u003e \u003cp\u003e1344\u003c/p\u003e \u003cp\u003e1441\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e62.3 (8.0) \u003c/p\u003e \u003cp\u003e62.2 (8.0) \u003c/p\u003e \u003cp\u003e62.8 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e956 (66.3)\u003c/p\u003e \u003cp\u003e961 (66.5) \u003c/p\u003e \u003cp\u003e944 (65.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1064 (73.8)\u003c/p\u003e \u003cp\u003e1060 (73.4)\u003c/p\u003e \u003cp\u003e1055 (73.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e35 (2.4)\u003c/p\u003e \u003cp\u003e32 (2.2)\u003c/p\u003e \u003cp\u003e38 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e262 (18.2)\u003c/p\u003e \u003cp\u003e270 (18.7)\u003c/p\u003e \u003cp\u003e263 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e81 (5.6)\u003c/p\u003e \u003cp\u003e83 (5.7)\u003c/p\u003e \u003cp\u003e87 (8.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCREDENCE,2018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFeb 17, 2014 to Oct 30, 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e240 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eCanagliflozin 100 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2199\u003c/p\u003e \u003cp\u003e2202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2174\u003c/p\u003e \u003cp\u003e2187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e63.2 (9.23)\u003c/p\u003e \u003cp\u003e62.9 (9.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1467 (66.7)\u003c/p\u003e \u003cp\u003e1440 (65.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1436 (65.3)\u003c/p\u003e \u003cp\u003e1476 (67.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e112 (5.1)\u003c/p\u003e \u003cp\u003e112 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e452 (20.6)\u003c/p\u003e \u003cp\u003e425 (19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e199 (9.0)\u003c/p\u003e \u003cp\u003e189 (8.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRosenstock J 2018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDec 13, 2013 to Aug 3, 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eErtugliflozin 5 mg\u003c/p\u003e \u003cp\u003eErtugliflozin 15 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.0 (6.3)\u003c/p\u003e \u003cp\u003e7.9 (6.1)\u003c/p\u003e \u003cp\u003e8.1 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e209 \u003c/p\u003e \u003cp\u003e207 \u003c/p\u003e \u003cp\u003e205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e175 \u003c/p\u003e \u003cp\u003e187 \u003c/p\u003e \u003cp\u003e180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56.5 (8.7)\u003c/p\u003e \u003cp\u003e56.6 (8.1)\u003c/p\u003e \u003cp\u003e56.9 (9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e98 (46.9) \u003c/p\u003e \u003cp\u003e97 (46.9) \u003c/p\u003e \u003cp\u003e93 (45.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e84.5(17.1)\u003c/p\u003e \u003cp\u003e84.8(17.2)\u003c/p\u003e \u003cp\u003e85.3(16.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e30.7 (4.7) \u003c/p\u003e \u003cp\u003e30.8 (4.8) \u003c/p\u003e \u003cp\u003e31.1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.4 (2.3) \u003c/p\u003e \u003cp\u003e9.3 (2.5) \u003c/p\u003e \u003cp\u003e9.3 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.2 (0.9)\u003c/p\u003e \u003cp\u003e 8.1 (0.9)\u003c/p\u003e \u003cp\u003e8.1 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e144 (68.9)\u003c/p\u003e \u003cp\u003e134 (64.7)\u003c/p\u003e \u003cp\u003e133 (64.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e19 (9.1) \u003c/p\u003e \u003cp\u003e22 (10.6)\u003c/p\u003e \u003cp\u003e23 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e31 (14.8) \u003c/p\u003e \u003cp\u003e34 (16.4)\u003c/p\u003e \u003cp\u003e35 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e15 (7.2)\u003c/p\u003e \u003cp\u003e17 (8.2)\u003c/p\u003e \u003cp\u003e14 (6.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eScott R 2018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOct 21, 2015 to Oct 10, 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSitagliptin 100 mg Dapagliflozin 5\u0026ndash;10 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.5 (7.0)\u003c/p\u003e \u003cp\u003e10.7\u0026thinsp;(7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e307\u003c/p\u003e \u003cp\u003e306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e299 \u003c/p\u003e \u003cp\u003e296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e67.7 (8.5)\u003c/p\u003e \u003cp\u003e66.6 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e169 (55.0)\u003c/p\u003e \u003cp\u003e186 (60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e87.4 (20.2) \u003c/p\u003e \u003cp\u003e88.7 (18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.8 (5.7)\u003c/p\u003e \u003cp\u003e31.5 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.0 (2.2)\u003c/p\u003e \u003cp\u003e9.2 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.7 (0.7)\u003c/p\u003e \u003cp\u003e7.8 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e240 (78.2) \u003c/p\u003e \u003cp\u003e234 (76.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e8 (2.6) \u003c/p\u003e \u003cp\u003e11 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e11 (3.6) \u003c/p\u003e \u003cp\u003e7 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e48 (15.7)\u003c/p\u003e \u003cp\u003e54 (17.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eYang W 2018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMar 31,2014 to Jan 28,2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u0026thinsp;+\u0026thinsp;Insulin\u003c/p\u003e \u003cp\u003eDapagliflozin 10 mg QD.PO\u0026thinsp;+\u0026thinsp;Insulin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.2 (6.7)\u003c/p\u003e \u003cp\u003e12.7 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e129\u003c/p\u003e \u003cp\u003e139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e125\u003c/p\u003e \u003cp\u003e135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.6 (8.9)\u003c/p\u003e \u003cp\u003e56.5 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e64 (48.1) \u003c/p\u003e \u003cp\u003e66 (47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e72.4 (13.1) \u003c/p\u003e \u003cp\u003e71.1 (12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e26.7 (3.3)\u003c/p\u003e \u003cp\u003e26.4 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.3 (2.2) \u003c/p\u003e \u003cp\u003e10.0 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.6 (0.8)\u003c/p\u003e \u003cp\u003e8.5 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1 (0.8) \u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e132 (99.2) \u003c/p\u003e \u003cp\u003e137 (98.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0 \u003c/p\u003e \u003cp\u003e2 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHollander P 2019\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDec 16, 2013 to Apr 18, 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eErtugliflozin 5mg\u003c/p\u003e \u003cp\u003eErtugliflozin 15mg\u003c/p\u003e \u003cp\u003eGlimepiride\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.3 (5.7) \u003c/p\u003e \u003cp\u003e7.5 (5.7) \u003c/p\u003e \u003cp\u003e7.6 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e445\u003c/p\u003e \u003cp\u003e435\u003c/p\u003e \u003cp\u003e435\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e339\u003c/p\u003e \u003cp\u003e340\u003c/p\u003e \u003cp\u003e327\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.7 (9.8) \u003c/p\u003e \u003cp\u003e58.0 (9.9) \u003c/p\u003e \u003cp\u003e57.9 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e227 (51.0) \u003c/p\u003e \u003cp\u003e191 (43.9) \u003c/p\u003e \u003cp\u003e224 (51.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e88.0 (19.0)\u003c/p\u003e \u003cp\u003e85.7 (19.1) 86.9 (20.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.7 (5.6)\u003c/p\u003e \u003cp\u003e 31.3 (6.2) \u003c/p\u003e \u003cp\u003e31.2 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.0 (1.9)\u003c/p\u003e \u003cp\u003e 9.0 (2.0) \u003c/p\u003e \u003cp\u003e8.8 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.8 (0.6) \u003c/p\u003e \u003cp\u003e7.8 (0.6) \u003c/p\u003e \u003cp\u003e7.8 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e329 (73.9) \u003c/p\u003e \u003cp\u003e311 (71.5) \u003c/p\u003e \u003cp\u003e317 (72.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e17 (3.8) \u003c/p\u003e \u003cp\u003e19 (4.4) \u003c/p\u003e \u003cp\u003e25 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e81 (18.2) \u003c/p\u003e \u003cp\u003e85 (19.5) \u003c/p\u003e \u003cp\u003e72 (16.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e18 (4.0) \u003c/p\u003e \u003cp\u003e20 (4.6) \u003c/p\u003e \u003cp\u003e21 (4.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRodbard HW 2019\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAug 10, 2016 to Mar 8, 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSemaglutide 14 mg\u003c/p\u003e \u003cp\u003eEmpagliflozin 25 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.2 (5.8)\u003c/p\u003e \u003cp\u003e7.7 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e411\u003c/p\u003e \u003cp\u003e410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e400\u003c/p\u003e \u003cp\u003e387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e57.0 (10.0)\u003c/p\u003e \u003cp\u003e58.0 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e205 (49.9) \u003c/p\u003e \u003cp\u003e201 (49.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e91.9 (20.5)\u003c/p\u003e \u003cp\u003e91.3 (20.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e32.9 (6.3)\u003c/p\u003e \u003cp\u003e 32.8 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.5 (2.3)\u003c/p\u003e \u003cp\u003e 9.7 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.1 (0.9)\u003c/p\u003e \u003cp\u003e 8.1 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e355 (86.4)\u003c/p\u003e \u003cp\u003e 353 (86.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e26 (6.3)\u003c/p\u003e \u003cp\u003e 33 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e28 (6.8)\u003c/p\u003e \u003cp\u003e 21 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e2 (0.5)\u003c/p\u003e \u003cp\u003e3 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eJi L 2019\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDec 16, 2015 to Dec 27, 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eErtugliflozin5mg\u003c/p\u003e \u003cp\u003eErtugliflozin15mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.4 (5.1) \u003c/p\u003e \u003cp\u003e7.0 (5.0) \u003c/p\u003e \u003cp\u003e7.5 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e167\u003c/p\u003e \u003cp\u003e170\u003c/p\u003e \u003cp\u003e169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e157\u003c/p\u003e \u003cp\u003e163\u003c/p\u003e \u003cp\u003e160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56.9 (9.0) \u003c/p\u003e \u003cp\u003e56.1 (9.0) \u003c/p\u003e \u003cp\u003e56.3 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e88 (52.7) \u003c/p\u003e \u003cp\u003e95 (55.9)\u003c/p\u003e \u003cp\u003e98 (58.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e70.1 (12.4) 71.4 (11.1) 69.5 (10.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e26.1 (3.4) \u003c/p\u003e \u003cp\u003e26.0 (2.8) \u003c/p\u003e \u003cp\u003e25.7 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.2 (2.1) \u003c/p\u003e \u003cp\u003e9.4 (2.0) \u003c/p\u003e \u003cp\u003e9.3 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.1 (1.0) \u003c/p\u003e \u003cp\u003e8.1 (0.9) \u003c/p\u003e \u003cp\u003e8.1 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e167 (100.0)\u003c/p\u003e \u003cp\u003e170 (100.0)\u003c/p\u003e \u003cp\u003e169 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHalvorsen YD 2019\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOct 12, 2017 to Oct 31, 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBexagliflozin 20 mg. \u003c/p\u003e \u003cp\u003eSitagliptin 100 mg.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.22 (5.7) 9.36 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e191\u003c/p\u003e \u003cp\u003e193\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e180\u003c/p\u003e \u003cp\u003e189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.3 (9.7) \u003c/p\u003e \u003cp\u003e59.6 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e120 (62.8) \u003c/p\u003e \u003cp\u003e126 (65.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e90.3 (20.7) \u003c/p\u003e \u003cp\u003e89.4 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e32.1 (6.1) \u003c/p\u003e \u003cp\u003e31.4 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.8 (2.3) \u003c/p\u003e \u003cp\u003e10.0 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.9 (0.8) \u003c/p\u003e \u003cp\u003e8.0 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e158 (82.7)\u003c/p\u003e \u003cp\u003e156 (80.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e6 (3.1) \u003c/p\u003e \u003cp\u003e2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e27 (14.1) \u003c/p\u003e \u003cp\u003e35 (18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFuchigami A 2020\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJuly 2017 to June 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDapaglifozin 5.0\u0026ndash;10mg \u003c/p\u003e \u003cp\u003eSitagliptin 50\u0026ndash;100 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.0 (6.4)\u003c/p\u003e \u003cp\u003e5.6 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e170\u003c/p\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e168\u003c/p\u003e \u003cp\u003e163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.3 (12.4)\u003c/p\u003e \u003cp\u003e57.9 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e104 (61.9)\u003c/p\u003e \u003cp\u003e95 (58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e74.5 (13.4)\u003c/p\u003e \u003cp\u003e74.9 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e27.8 (4.0) \u003c/p\u003e \u003cp\u003e27.9 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.4 (1.86) \u003c/p\u003e \u003cp\u003e8.4 (1.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.8 (0.8) \u003c/p\u003e \u003cp\u003e7.8 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e170 (100.0)\u003c/p\u003e \u003cp\u003e170 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKatakami N 2020\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJan 12, 2016. and Nov 25, 2016.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTofoglifozin 20 mg use drugs other than SGLT2 inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.1 (8.4)\u003c/p\u003e \u003cp\u003e12.5 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e169\u003c/p\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e140\u003c/p\u003e \u003cp\u003e147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e61.3 (9.3)\u003c/p\u003e \u003cp\u003e60.9 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e99 (58.6) \u003c/p\u003e \u003cp\u003e99 (58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e27.0 (5.8\u003c/p\u003e \u003cp\u003e27.0 (4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e7.8 (1.7)\u003c/p\u003e \u003cp\u003e7.8 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.4 (0.7)\u003c/p\u003e \u003cp\u003e7.3 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eJabbour SA 2020\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSept 4, 2014 to Dec 28, 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eExenatide 2mg plus Dapagliflozin 10 mg \u003c/p\u003e \u003cp\u003eexenatide 2mg plus Placebo\u003c/p\u003e \u003cp\u003eDapagliflozin 10mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.6 (6.0)\u003c/p\u003e \u003cp\u003e7.4 (5.5)\u003c/p\u003e \u003cp\u003e7.1 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e233 \u003c/p\u003e \u003cp\u003e231 \u003c/p\u003e \u003cp\u003e231\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e155 \u003c/p\u003e \u003cp\u003e154 \u003c/p\u003e \u003cp\u003e136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e53.8 (9.8)\u003c/p\u003e \u003cp\u003e54.2 (9.6)\u003c/p\u003e \u003cp\u003e54.5 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e102 (44.7)\u003c/p\u003e \u003cp\u003e116 (51.1) \u003c/p\u003e \u003cp\u003e110 (47.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e91.8 (22.2)\u003c/p\u003e \u003cp\u003e89.8 (20.2)\u003c/p\u003e \u003cp\u003e91.1 (19.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e33.2 (6.8)\u003c/p\u003e \u003cp\u003e32.0 (5.9)\u003c/p\u003e \u003cp\u003e33.0 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e11.0 (3.0)\u003c/p\u003e \u003cp\u003e10.7 (2.8)\u003c/p\u003e \u003cp\u003e10.6 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e9.3 (1.1)\u003c/p\u003e \u003cp\u003e9.3 (1.1)\u003c/p\u003e \u003cp\u003e9.3 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e190 (83.3)\u003c/p\u003e \u003cp\u003e194 (85.5)\u003c/p\u003e \u003cp\u003e189 (82.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e34 (14.9)\u003c/p\u003e \u003cp\u003e27 (11.9)\u003c/p\u003e \u003cp\u003e33 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e3 (1.3)\u003c/p\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e96 (42.1)\u003c/p\u003e \u003cp\u003e96 (42.3)\u003c/p\u003e \u003cp\u003e92 (42.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAllegretti AS 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSept 23, 2016 to Jan 11, 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eBexagliflozin 20 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e155\u003c/p\u003e \u003cp\u003e157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e144\u003c/p\u003e \u003cp\u003e152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e69.9 (8.3)\u003c/p\u003e \u003cp\u003e69.3 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e104 (67.1)\u003c/p\u003e \u003cp\u003e92 (58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e88 (56.8)\u003c/p\u003e \u003cp\u003e83 (52.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e6 (3.9)\u003c/p\u003e \u003cp\u003e9 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e59 (38.1)\u003c/p\u003e \u003cp\u003e61 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e2 (1.3)\u003c/p\u003e \u003cp\u003e4 (2.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBEST 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOct 12, 2015 to Oct 23, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eBexagliflozin 20 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.2 (9.3)\u003c/p\u003e \u003cp\u003e14.9 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e567\u003c/p\u003e \u003cp\u003e1133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e482\u003c/p\u003e \u003cp\u003e987\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e64.6 (8.0)\u003c/p\u003e \u003cp\u003e64.4 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e390 (68.8)\u003c/p\u003e \u003cp\u003e792 (69.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e92.6 (20.0)\u003c/p\u003e \u003cp\u003e94.6 (21.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e32.2 (5.8)\u003c/p\u003e \u003cp\u003e32.8 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.3 (1.0)\u003c/p\u003e \u003cp\u003e8.3 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e430 (75.8)\u003c/p\u003e \u003cp\u003e879 (77.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e28 (4.9)\u003c/p\u003e \u003cp\u003e46 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e55 (9.7)\u003c/p\u003e \u003cp\u003e108 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e54 (9.5)\u003c/p\u003e \u003cp\u003e100 (8.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSOTA-BONE 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFeb 19, 2018 to May 30, 2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eSotagliflozin 200 mg \u003c/p\u003e \u003cp\u003eSotagliflozin 400 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e104 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e126 \u003c/p\u003e \u003cp\u003e125 \u003c/p\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9 \u003c/p\u003e \u003cp\u003e9 \u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e66.3 (5.7) \u003c/p\u003e \u003cp\u003e66.1 (6.7) \u003c/p\u003e \u003cp\u003e66.5 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e70 (55.6) \u003c/p\u003e \u003cp\u003e69 (55.2) \u003c/p\u003e \u003cp\u003e70 (56.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.4 (0.9) \u003c/p\u003e \u003cp\u003e8.3 (0.9) \u003c/p\u003e \u003cp\u003e8.3 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e88 (69.8)\u003c/p\u003e \u003cp\u003e87 (69.6)\u003c/p\u003e \u003cp\u003e88 (70.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e8 (6.3)\u003c/p\u003e \u003cp\u003e8 (6.4)\u003c/p\u003e \u003cp\u003e6 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e26 (20.6)\u003c/p\u003e \u003cp\u003e25 (20.0)\u003c/p\u003e \u003cp\u003e24 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e4 (3.1)\u003c/p\u003e \u003cp\u003e5 (4.0)\u003c/p\u003e \u003cp\u003e7 (5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNCT02769481 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAug 15, 2016 to Jun 14, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBexagliflozin 20 mg Glimepiride 2, 4 or 6 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e96 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e213\u003c/p\u003e \u003cp\u003e213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e180\u003c/p\u003e \u003cp\u003e177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.5 (9.1) 59.7 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e118 (55.4)\u003c/p\u003e \u003cp\u003e130 (61.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e88.0 (19.1)\u003c/p\u003e \u003cp\u003e90.2 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.5 (4.9)\u003c/p\u003e \u003cp\u003e32.2 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e198 (93.0)\u003c/p\u003e \u003cp\u003e204 (95.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e5 (2.3)\u003c/p\u003e \u003cp\u003e4 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e9 (4.2)\u003c/p\u003e \u003cp\u003e4 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNCT02926950 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNov 1, 2016 to Mar 22, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u0026thinsp;+\u0026thinsp;Metformin \u003c/p\u003e \u003cp\u003eSotagliflozin 400 mg\u0026thinsp;+\u0026thinsp;Metformin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e79 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e259 \u003c/p\u003e \u003cp\u003e259\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e210 \u003c/p\u003e \u003cp\u003e211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.9 (9.4) \u003c/p\u003e \u003cp\u003e60.0 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e146 (56.4) \u003c/p\u003e \u003cp\u003e142 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.2 (0.8) \u003c/p\u003e \u003cp\u003e8.2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e197 (76.1)\u003c/p\u003e \u003cp\u003e223 (86.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e40 (15.4)\u003c/p\u003e \u003cp\u003e28 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e19 (7.3)\u003c/p\u003e \u003cp\u003e6 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e3 (1.2)\u003c/p\u003e \u003cp\u003e2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNCT03066830 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFeb 24, 2017 to Apr 30, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eSotagliflozin 400 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e254 \u003c/p\u003e \u003cp\u003e253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e221 \u003c/p\u003e \u003cp\u003e231\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e63.0 (9.9) \u003c/p\u003e \u003cp\u003e63.3 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e130 (51.2) \u003c/p\u003e \u003cp\u003e149 (58.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.18 (0.83) \u003c/p\u003e \u003cp\u003e8.20 (0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e211 (83.1)\u003c/p\u003e \u003cp\u003e215 (85.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e8 (3.1)\u003c/p\u003e \u003cp\u003e8 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e34 (13.4)\u003c/p\u003e \u003cp\u003e28 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003cp\u003e2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSOTA-GLIM 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDec 1, 2017 to Sept 6, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eSotagliflozin 400 mg \u003c/p\u003e \u003cp\u003eSotagliflozin 200 mg \u003c/p\u003e \u003cp\u003eGlimepiride\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e159 \u003c/p\u003e \u003cp\u003e317 \u003c/p\u003e \u003cp\u003e160 \u003c/p\u003e \u003cp\u003e318\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e125 \u003c/p\u003e \u003cp\u003e266 \u003c/p\u003e \u003cp\u003e128 \u003c/p\u003e \u003cp\u003e270\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.8 (11.2) \u003c/p\u003e \u003cp\u003e59.7 (10.4) \u003c/p\u003e \u003cp\u003e58.6 (9.9) \u003c/p\u003e \u003cp\u003e59.8 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e82 (51.6)\u003c/p\u003e \u003cp\u003e160 (50.5)\u003c/p\u003e \u003cp\u003e85 (53.1)\u003c/p\u003e \u003cp\u003e175 (55.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.1 (0.7) \u003c/p\u003e \u003cp\u003e8.1 (0.8)\u003c/p\u003e \u003cp\u003e8.1 (0.8)\u003c/p\u003e \u003cp\u003e8.1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e141 (88.7)\u003c/p\u003e \u003cp\u003e269 (84.9)\u003c/p\u003e \u003cp\u003e136 (85.0)\u003c/p\u003e \u003cp\u003e277 (87.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e13 (8.2)\u003c/p\u003e \u003cp\u003e34 (10.7)\u003c/p\u003e \u003cp\u003e19 (11.9)\u003c/p\u003e \u003cp\u003e36 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e3 (1.9)\u003c/p\u003e \u003cp\u003e5 (1.6)\u003c/p\u003e \u003cp\u003e3 (1.9)\u003c/p\u003e \u003cp\u003e4 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e2 (1.2)\u003c/p\u003e \u003cp\u003e9 (2.8)\u003c/p\u003e \u003cp\u003e2 (1.3)\u003c/p\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSOTA-EMPA 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNov 27, 2017 to May 16, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eSotagliflozin 400 mg \u003c/p\u003e \u003cp\u003eEmpagliflozin 25 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e154\u003c/p\u003e \u003cp\u003e307 \u003c/p\u003e \u003cp\u003e309\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e147\u003c/p\u003e \u003cp\u003e293 \u003c/p\u003e \u003cp\u003e292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.8 (9.6)\u003c/p\u003e \u003cp\u003e58.9 (9.7) \u003c/p\u003e \u003cp\u003e59.7 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e97 (51.3)\u003c/p\u003e \u003cp\u003e166 (54.1)\u003c/p\u003e \u003cp\u003e151 (48.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.2 (0.8) \u003c/p\u003e \u003cp\u003e8.2 (0.9)\u003c/p\u003e \u003cp\u003e8.2 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e137 (89.0)\u003c/p\u003e \u003cp\u003e256 (83.4)\u003c/p\u003e \u003cp\u003e257 (83.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e5 (3.2)\u003c/p\u003e \u003cp\u003e13 (4.2)\u003c/p\u003e \u003cp\u003e13 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e4 (2.6)\u003c/p\u003e \u003cp\u003e17 (5.5)\u003c/p\u003e \u003cp\u003e11 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e8 (5.2)\u003c/p\u003e \u003cp\u003e21 (6.9)\u003c/p\u003e \u003cp\u003e28 (9.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSOTA-INS 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSept 15, 2017 to Sept 17, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eSotagliflozin 200 mg \u003c/p\u003e \u003cp\u003eSotagliflozin 400 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e144 \u003c/p\u003e \u003cp\u003e141 \u003c/p\u003e \u003cp\u003e286\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e129 \u003c/p\u003e \u003cp\u003e130 \u003c/p\u003e \u003cp\u003e249\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e62.2 (8.9) \u003c/p\u003e \u003cp\u003e62.1 (10.2)\u003c/p\u003e \u003cp\u003e62.7 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e86 (59.7)\u003c/p\u003e \u003cp\u003e76 (53.9)\u003c/p\u003e \u003cp\u003e154 (53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.8 (0.8)\u003c/p\u003e \u003cp\u003e8.8 (0.8)\u003c/p\u003e \u003cp\u003e8.7 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e117 (81.3)\u003c/p\u003e \u003cp\u003e124 (87.9)\u003c/p\u003e \u003cp\u003e234 (81.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e10 (6.9)\u003c/p\u003e \u003cp\u003e10 (7.1)\u003c/p\u003e \u003cp\u003e27 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e9 (6.3)\u003c/p\u003e \u003cp\u003e1 (0.7)\u003c/p\u003e \u003cp\u003e6 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e8 (5.5)\u003c/p\u003e \u003cp\u003e6 (4.3)\u003c/p\u003e \u003cp\u003e19 (6.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCherney DZI 2021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAug 16, 2017 to Dec 11, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eSotagliflozin 200 mg\u003c/p\u003e \u003cp\u003eSotagliflozin 400 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56.3 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e93\u003c/p\u003e \u003cp\u003e92\u003c/p\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e75 \u003c/p\u003e \u003cp\u003e78 \u003c/p\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e68.0 (8.3) \u003c/p\u003e \u003cp\u003e66.8 (10.0) \u003c/p\u003e \u003cp\u003e67.3 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e44 (47.8) \u003c/p\u003e \u003cp\u003e49 (53.3) \u003c/p\u003e \u003cp\u003e35 (48.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.7 (5.7) \u003c/p\u003e \u003cp\u003e30.9 (5.4) \u003c/p\u003e \u003cp\u003e32.1 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.7 (3.2) \u003c/p\u003e \u003cp\u003e8.8 (3.3) \u003c/p\u003e \u003cp\u003e8.2 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.4 (1.1) \u003c/p\u003e \u003cp\u003e8.3 (1.0) \u003c/p\u003e \u003cp\u003e8.3 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e76 (81.7) \u003c/p\u003e \u003cp\u003e73 (79.3) \u003c/p\u003e \u003cp\u003e78 (84.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e6 (6.5) \u003c/p\u003e \u003cp\u003e7 (7.6) \u003c/p\u003e \u003cp\u003e3 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e1 (1.1) \u003c/p\u003e \u003cp\u003e2 (2.2) \u003c/p\u003e \u003cp\u003e2 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e51 (58.4)\u003c/p\u003e \u003cp\u003e43 (46.8)\u003c/p\u003e \u003cp\u003e42 (45.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWada T 2022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFeb 15, 2018 to Jan 21, 2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCanagliflozin 100mg \u003c/p\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.4 (8.6)\u003c/p\u003e \u003cp\u003e16.5 (9.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e154\u003c/p\u003e \u003cp\u003e154\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e124\u003c/p\u003e \u003cp\u003e127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e62.5 (10.5)\u003c/p\u003e \u003cp\u003e62.4 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e115 (74.7)\u003c/p\u003e \u003cp\u003e129 (83.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e26.7 (4.4) \u003c/p\u003e \u003cp\u003e27.1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.8 (1.1)\u003c/p\u003e \u003cp\u003e7.8 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e154 (100) \u003c/p\u003e \u003cp\u003e154 (100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTakeshita Y 2022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMar 2016 to Dec 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTofogliflozin 20mg\u003c/p\u003e \u003cp\u003eGlimepiride 0.8mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.0 (16.1)\u003c/p\u003e \u003cp\u003e50.5 (19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7 (35,0)\u003c/p\u003e \u003cp\u003e14 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e79.3 (18.2)\u003c/p\u003e \u003cp\u003e84.7 (25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e31.0 (6.7)\u003c/p\u003e \u003cp\u003e32.0 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.0 (2.3)\u003c/p\u003e \u003cp\u003e7.8 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.9 (1.1)\u003c/p\u003e \u003cp\u003e8.2 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e20 (100.0)\u003c/p\u003e \u003cp\u003e20 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCherney DZI 2023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAug 16, 2017 to Oct 25, 2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo \u003c/p\u003e \u003cp\u003eSotagliflozin 200 mg \u003c/p\u003e \u003cp\u003eSotagliflozin 400 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.7 (9.5)\u003c/p\u003e \u003cp\u003e17.2 (9.3)\u003c/p\u003e \u003cp\u003e16.3 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e260 \u003c/p\u003e \u003cp\u003e263 \u003c/p\u003e \u003cp\u003e264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e224 \u003c/p\u003e \u003cp\u003e240 \u003c/p\u003e \u003cp\u003e232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e69.3 (8.1) \u003c/p\u003e \u003cp\u003e69.6 (7.5) \u003c/p\u003e \u003cp\u003e69.5 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e149 (57.3)\u003c/p\u003e \u003cp\u003e143 (54.4)\u003c/p\u003e \u003cp\u003e152 (57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e32.5 (5.2) \u003c/p\u003e \u003cp\u003e32.3 (5.7) \u003c/p\u003e \u003cp\u003e32.4 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e9.2 (3.3) \u003c/p\u003e \u003cp\u003e9.1 (2.7)\u003c/p\u003e \u003cp\u003e9.0 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e8.3 (1.0) \u003c/p\u003e \u003cp\u003e8.3 (0.9) \u003c/p\u003e \u003cp\u003e8.3 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e220 (84.6) \u003c/p\u003e \u003cp\u003e231 (87.8) \u003c/p\u003e \u003cp\u003e215 (81.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e12 (4.6) \u003c/p\u003e \u003cp\u003e14 (5.3) \u003c/p\u003e \u003cp\u003e15 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e5 (1.9) \u003c/p\u003e \u003cp\u003e7 (2.7) \u003c/p\u003e \u003cp\u003e8 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e23 (8.8)\u003c/p\u003e \u003cp\u003e11 (4.2)\u003c/p\u003e \u003cp\u003e26 (9.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHerrington WG 2023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJan 31, 2019 to Jul 2, 2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e162 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003cp\u003eEmpagliflozin 10 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3305 \u003c/p\u003e \u003cp\u003e3304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2457 \u003c/p\u003e \u003cp\u003e2549\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e63.8 (13.9)\u003c/p\u003e \u003cp\u003e63.9 (13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2207 (66.8)\u003c/p\u003e \u003cp\u003e2210 (66.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e29.8 (6.8)\u003c/p\u003e \u003cp\u003e 29.7 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1920 (58.1)\u003c/p\u003e \u003cp\u003e1939 (58.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e134 (4.1)\u003c/p\u003e \u003cp\u003e128 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e1199 (36.3)\u003c/p\u003e \u003cp\u003e1194 (36.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e52 (1.6)\u003c/p\u003e \u003cp\u003e43 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eShimoda M 2024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eApr 1, 2019 to Dec 31,2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLuseogliflozin 2.5mg Teneligliptin 20mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.1 (7.9) \u003c/p\u003e \u003cp\u003e9.2 (7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e49\u003c/p\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e44\u003c/p\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60.8 (11.1)\u003c/p\u003e \u003cp\u003e62.6 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e26 (53.1)\u003c/p\u003e \u003cp\u003e31 (57.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e69.9 (12.3) \u003c/p\u003e \u003cp\u003e71.9 (19.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e27.0 (4.2) \u003c/p\u003e \u003cp\u003e27.2 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.3 (1.3)\u003c/p\u003e \u003cp\u003e8.2 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7.6 (0.4) \u003c/p\u003e \u003cp\u003e7.5 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003e49 (100.0)\u003c/p\u003e \u003cp\u003e54 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c17\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eGI neoplasm risk and SGLT2 inhibitors\u003c/h3\u003e\n\u003cp\u003eControl groups received either placebo or alternative antihyperglycemic agents, and pooled results revealed no significant elevation in GI neoplasm risk among SGLT2 inhibitor users compared with non-SGLT2 treatments (OR\u0026thinsp;=\u0026thinsp;1.10, 95% CI 0.84\u0026ndash;1.44; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.46, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSite-specific outcomes\u003c/h2\u003e \u003cp\u003eSite-specific analyses revealed no statistically significant associations between SGLT2 inhibitor use and the risk of any individual GI neoplasms. The odds ratios with 95% confidence intervals were as follows: esophageal (OR\u0026thinsp;=\u0026thinsp;1.12, 95% CI 0.37\u0026ndash;3.45), gastric (1.20, 0.65\u0026ndash;2.23), hepatic (0.62, 0.31\u0026ndash;1.22), pancreatic (0.93, 0.52\u0026ndash;1.66), colonic (1.28, 0.78\u0026ndash;2.08), colorectal (0.76, 0.27\u0026ndash;2.17), or rectal neoplasms (0.98, 0.49\u0026ndash;1.97) (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Supplementary eFigure 2). In all cases, the confidence intervals crossed the null value, indicating no consistent site-specific signal of increased or decreased risk. The point estimates and interval widths suggest that any true effect, if present, is likely to be small in magnitude.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDrug-specific analyses\u003c/h2\u003e \u003cp\u003eSubgroup analyses by individual SGLT2 inhibitors identified no statistically significant association with gastrointestinal neoplasm risk for any agent. The odds ratios (95% CI) were as follows: canagliflozin, 1.02 (0.68\u0026ndash;1.52); dapagliflozin, 1.29 (0.56\u0026ndash;2.98); empagliflozin, 1.23 (0.70\u0026ndash;2.19); ertugliflozin, 1.32 (0.39\u0026ndash;4.46); tofogliflozin, 1.10 (0.32\u0026ndash;3.72); and bexagliflozin, 0.85 (0.27\u0026ndash;2.62) (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05; eFigure 3). These findings suggest that none of the studied SGLT2 inhibitors confer a distinct advantage or harm with respect to GI neoplasm risk within the available trial data.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eClinical subgroups\u003c/h2\u003e \u003cp\u003eSubgroup analyses were conducted according to baseline age, BMI, treatment duration, baseline HbA1c, and drug dosage. The pooled odds ratios with 95% confidence intervals across all these subgroups were consistently centered around the null value, with no consistent or clinically meaningful effect modification observed (Supplementary eFigures 4\u0026ndash;10). Across prespecified subgroups (agent, dose, exposure duration, age, BMI, baseline HbA1c), pooled ORs clustered around unity, and interaction \u003cem\u003ep\u003c/em\u003e-values were non-significant, indicating no reproducible effect modification (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In summary, no clearly identifiable high- or low-risk patient subgroup emerged from these analyses. Future studies with longer follow-up and a greater number of endpoint events will be required to detect potential subtle effect modifiers.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003ePublication bias\u003c/h2\u003e \u003cp\u003eEgger\u0026rsquo;s test showed no evidence of publication bias (p\u0026thinsp;=\u0026thinsp;0.15; t\u0026thinsp;=\u0026thinsp;1.46). The funnel plot was largely symmetrical, indicating little evidence of publication bias (Supplementary eFigures 11\u0026ndash;28).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis comprehensive meta-analysis of 49 RCTs involving 49,054 patients with T2DM provides robust evidence that SGLT2 inhibitor therapy is not associated with an increased risk of gastrointestinal neoplasms (OR 1.10, 95% CI 0.84\u0026ndash;1.44). The neutral signal was consistent across GI subsites, agents, and treatment durations. Dose-stratified analyses showed no association between SGLT2 inhibitors and GI neoplasms and no discernible dose\u0026ndash;response within approved dosing ranges. Together, these results indicate that, at recommended doses used in contemporary trials, SGLT2 inhibitors were not associated with GI neoplasm risk, supporting the safety of currently recommended dosing with respect to GI neoplasm incidence. Subgroups were prespecified on biological and methodological grounds\u0026mdash;BMI (adiposity-related inflammation); HbA1c (glycemic/hyperinsulinemic burden); exposure duration (latency; \u0026le;52, 52\u0026ndash;104, \u0026gt;\u0026thinsp;104 weeks); dose (FDA-labeled low vs high; potential dose\u0026ndash;response); and agent (drug-specific selectivity or off-target effects). Across strata, pooled ORs centered on 1.0 with 95% CIs spanning unity, and interaction p-values were non-significant, indicating no reproducible effect modification.\u003c/p\u003e \u003cp\u003eMechanistically, SGLT2 inhibitors are proposed to engage several anticancer pathways, such as reducing hyperinsulinemia, attenuating systemic inflammation, and limiting glucose availability for tumors through urinary glucose excretion (68). Indeed, improvements in insulin sensitivity have been documented in meta-analyses, with more consistent effects observed for agents like dapagliflozin (69). Preclinical models further suggest that certain SGLT2 inhibitors may directly inhibit cancer cell glucose uptake (70). However, despite these plausible mechanisms, our synthesis of RCT data\u0026mdash;under current clinical dosing and follow-up durations\u0026mdash;did not show a measurable reduction in GI cancer incidence. This disconnect likely stems from several factors: (i) the drug concentrations required for direct antitumor effects in vitro often exceed plasma levels achieved with standard human dosing (71); (ii) the complex, multifactorial nature of human carcinogenesis\u0026mdash;shaped by immune surveillance, the tumor microenvironment, and long-term adaptation\u0026mdash;is not fully captured by animal or cell models (72); and (iii) the insufficient duration of RCTs, which may preclude the detection of slow, latency-dependent effects. Thus, while preclinical data outline plausible pathways, they have not translated into a clinically meaningful reduction in GI cancer risk, underscoring the need for longer, cancer-endpoint trials.\u003c/p\u003e \u003cp\u003eThe neutral findings from our RCT-based meta-analysis contrast with results from several large real-world observational studies suggesting lower risks for certain GI neoplasms with SGLT2 inhibitors. In a population-based study in Gastric Cancer, initiation of SGLT2 inhibitors was associated with a substantially reduced incidence of gastric cancer versus DPP-4 inhibitors (adjusted HR\u0026thinsp;=\u0026thinsp;0.30) (13). A cohort from China\u0026rsquo;s Taiwan region likewise reported a lower overall cancer risk (HR 0.90, 95% CI 0.87\u0026ndash;0.93), with favorable estimates for GI neoplasms (esophageal HR 0.57; colorectal/liver HR 0.90) (73). However, other real-world evidence\u0026mdash;including quantitative overviews of reviews\u0026mdash;has not shown a class-wide reduction in total or most site-specific cancers, and several population-based analyses report null associations after extensive adjustment. Taken together, observational results are heterogeneous: some signals suggest site-specific benefit, while others are neutral. Given the inherent limitations of nonrandomized designs (residual confounding by indication, immortal-time bias, differential screening, and unmeasured lifestyle factors), our RCT synthesis\u0026mdash;though limited by relatively short follow-up\u0026mdash;provides the highest internal validity and does not support a clinically meaningful reduction in GI cancer incidence within current trial durations. Longer RCTs with cancer endpoints, or rigorously specified target-trial emulations, are needed to verify or refute these real-world signals (74).\u003c/p\u003e \u003cp\u003eFrom a safety perspective, our findings that GI neoplasms are not increased with SGLT2 inhibitor use further solidify the overall safety profile of this drug class. It is well-established that SGLT2 inhibitors are associated with an increased risk of genital mycotic infections, though these are typically manageable (75). Other risks, such as volume depletion and rare diabetic ketoacidosis events, are also recognized and can be mitigated with appropriate patient selection and monitoring (76, 77). Crucially, large outcome trials have consistently demonstrated significant cardiorenal benefits that, for most patients with T2DM, outweigh these known risks (78). Thus, our results provide reassurance that GI cancer risk does not appear to be a material safety concern for this class, supporting their continued use in clinical practice.\u003c/p\u003e \u003cp\u003eTo align our results with the current evidence base, we assessed concordance with two recent high-level syntheses. Xu et al. meta-analyzed 59 randomized controlled trials (n\u0026thinsp;=\u0026thinsp;113,909) and found no significant effect of SGLT2 inhibitors on overall cancer (RR 1.01, 95% CI 0.94\u0026ndash;1.08) or on gastrointestinal cancer (RR 1.02, 95% CI 0.85\u0026ndash;1.22), consistent with our neutral primary results (79). Our analysis extends this evidence by focusing specifically on GI neoplasms with finer site granularity (esophageal, gastric, hepatic, pancreatic, colonic, colorectal, rectal, and biliary), incorporating more recent RCTs (through March 17, 2025), and reporting prespecified subgroup analyses (agent, FDA-labeled dose, exposure duration\u0026thinsp;\u0026le;\u0026thinsp;52, 52\u0026ndash;104, \u0026gt;\u0026thinsp;104 weeks, age, BMI, HbA1c) with interaction p-values, alongside sensitivity analyses and Egger\u0026rsquo;s tests. In a complementary overview of reviews, Pelletier et al. concluded that SGLT2 inhibitors as a class are not associated with increased risk of total or most site-specific neoplasms, while noting inconsistent drug-specific signals and substantial variability in methodological quality across reviews (80). Apparent differences from our findings likely reflect scope and design heterogeneity in that overview (e.g., pooled observational with randomized evidence, variable endpoint definitions, overlapping evidence bases, and differing follow-up windows), whereas our analysis is restricted to RCTs, harmonizes GI site definitions, and standardizes subgroup cut-points. Taken together, these syntheses corroborate our overall neutral conclusion for GI neoplasm risk and underscore the need for longer, cancer-endpoint RCTs to clarify any drug- or duration-dependent effects.\u003c/p\u003e \u003cp\u003eThis study has limitations. First, although randomization is intended to balance confounding, cancer was captured as a secondary outcome in most included RCTs; key baseline oncogenic risk factors (e.g., smoking, alcohol use, family history, prior screening) were variably measured and inconsistently reported across groups, leaving the possibility of residual confounding despite randomization. Second, the evaluation of long-term carcinogenicity is constrained by short follow-up: nearly half of the trials (47%) followed participants for \u0026le;\u0026thinsp;1 year, which may be insufficient to detect latency-dependent or cumulative exposure effects on GI neoplasms. Third, to maintain currency, we cite very recent studies (2024\u0026ndash;2025); while this strengthens timeliness, some estimates may be based on immature follow-up and require confirmation with longer observation. These considerations temper the interpretation of the neutral findings and underscore the need for longer RCTs with prespecified cancer endpoints and standardized collection of baseline cancer risk factors.\u003c/p\u003e \u003cp\u003eIn conclusion, SGLT2 inhibitor treatment in adults with T2DM was not linked to an altered incidence of gastrointestinal neoplasms over the durations captured by the available trials, with consistent results across agents and anatomical subsites. The aggregate evidence supports intermediate-term oncologic safety and continued therapeutic use. Clarification of long-term risk should come from extended surveillance cohorts and dedicated cancer-endpoint studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eSGLT2 \u0026nbsp; \u0026nbsp; \u0026nbsp; Sodium-glucose cotransporter 2\u003c/p\u003e\n\u003cp\u003eGLP-1 \u0026nbsp; \u0026nbsp; \u0026nbsp;Glucagon-like peptide-1\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDPP-4 \u0026nbsp; \u0026nbsp; \u0026nbsp;Dipeptidyl peptidase-4\u003c/p\u003e\n\u003cp\u003eGI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Gastrointestinal\u003c/p\u003e\n\u003cp\u003eORs \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Odds ratios\u003c/p\u003e\n\u003cp\u003eRR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Risk Ratio\u003c/p\u003e\n\u003cp\u003eCIs \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Confidence intervals\u003c/p\u003e\n\u003cp\u003eHR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Hazard Ratio\u003c/p\u003e\n\u003cp\u003eI² \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;I-squared statistic\u003c/p\u003e\n\u003cp\u003eSD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Standard Deviation\u003c/p\u003e\n\u003cp\u003eRoB 2 \u0026nbsp; \u0026nbsp; \u0026nbsp;Risk of Bias 2 tool\u003c/p\u003e\n\u003cp\u003eRCTs \u0026nbsp; \u0026nbsp; \u0026nbsp; Randomized controlled trials\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eT2DM \u0026nbsp; \u0026nbsp; \u0026nbsp; Type 2 diabetes\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Body mass index\u003c/p\u003e\n\u003cp\u003eHbA1c \u0026nbsp; \u0026nbsp; \u0026nbsp;Glycated hemoglobin\u003c/p\u003e\n\u003cp\u003eCENTRAL \u0026nbsp; Cochrane Central Register of Controlled Trials\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eAll the authors have provided their consent for publication of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u0026nbsp;\u003c/strong\u003eThe authors confirm that the data supporting the findings of this study are available within the article and the supplementary material.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare they have no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis work was supported by the Natural Science Foundation of China (grant numbers: 82300911, 32201056), Sichuan Province Science and Technology Program (application number: 2025ZNSFSC0741, 2025ZNSFSC1622), and Scientific Research Funding of Luzhou-Southwest Medical University (application number: 25YKDJCYJ0224).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT authorship contribution statement:\u003c/strong\u003e \u003cstrong\u003eYu-Fan Zhang\u003c/strong\u003e: investigation, software, data curation, writing-original draft, writing-review \u0026amp; editing;\u0026nbsp;\u003cstrong\u003eJia-Jie Xie\u003c/strong\u003e: data curation, methodology, software; \u003cstrong\u003eQi Wu\u003c/strong\u003e: investigation, methodology;\u0026nbsp;\u003cstrong\u003eXiao-Yu Zhou\u003c/strong\u003e: methodology;\u003cstrong\u003e\u0026nbsp;Chen Zeng\u003c/strong\u003e: software;\u0026nbsp;\u003cstrong\u003eYan Zeng\u003c/strong\u003e:\u0026nbsp;validation; \u003cstrong\u003eYi-Meng He\u003c/strong\u003e: software;\u0026nbsp;\u003cstrong\u003eMan Guo\u003c/strong\u003e: conceptualization, resources, funding acquisition, supervision, writing-review \u0026amp; editing; \u003cstrong\u003eFang-Yuan Teng\u003c/strong\u003e: funding acquisition, resources, writing-review \u0026amp; editing; \u003cstrong\u003eYong Xu\u003c/strong\u003e: funding acquisition, supervision, resources, writing-review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Zhang H, Jia Q, Song P, Li Y, Jiang L, Fu X, Li S. 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Efficacy and safety of canagliflozin as add-on therapy to teneligliptin in Japanese patients with type 2 diabetes mellitus: Results of a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes, obesity \u0026amp; metabolism. 2017;19(6):874\u0026thinsp;\u0026minus;\u0026thinsp;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Ji, L., Ma, J., Li, H., Mansfield, T., T'Joen, C.L., Iqbal, N., et al.. Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III study. Clinical therapeutics. 2014;36(1):84\u0026ndash;100.e9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Neal, B., Perkovic, V., Matthews, D., Mahaffey, K., Fulcher, G., Meininger, G., et al.. Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R): A randomized, placebo-controlled trial. Diabetes, obesity \u0026amp; metabolism. 2017;19(3):387\u0026thinsp;\u0026minus;\u0026thinsp;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Development JR. A Study of the Effects of Canagliflozin (JNJ-28431754) on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus (CANVAS-R) 2017 [Available from: https://clinicaltrials.gov/study/NCT02465515.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Jardine, M., Mahaffey, K., Neal, B., Agarwal, R., Bakris, G., Brenner, B., et al.. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics. American journal of nephrology. 2017;46(6):462\u0026thinsp;\u0026minus;\u0026thinsp;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Lock JP. 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Efficacy and Safety of Sotagliflozin Versus Placebo and Empagliflozin in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking a DPP4 Inhibitor Alone or With Metformin (SOTA-EMPA) 2019 [Available from: https://clinicaltrials.gov/study/NCT03351478?cond=NCT03351478\u0026amp;rank=1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Pandey, A., Alcaraz, M., Jr, Saggese, P., Soto, A., Gomez, E., et al.. Exploring the Role of SGLT2 Inhibitors in Cancer: Mechanisms of Action and Therapeutic Opportunities. Cancers. 2025;17(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Fakhrolmobasheri, M., Abhari, A., Manshaee, B., Heidarpour, M., Shafie, D., Mohammadbeigi, E., et al.. Effect of sodium-glucose cotransporter 2 inhibitors on insulin resistance; a systematic review and meta-analysis. Acta Diabetol. 2023;60(2):191\u0026ndash;202.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Dong W, Wang Y, Fan S.. 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Comparison between sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase 4 inhibitors on the risk of incident cancer in patients with diabetes mellitus: A real-world evidence study. Diabetes/metabolism research and reviews. 2024;40(3):e3784.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Tang, H., Dai, Q., Shi, W., Zhai, S., Song, Y., Han, J.. SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Diabetologia. 2017;60(10):1862-72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Kittipibul, V., Cox, Z., Chesdachai, S., Fiuzat, M., Lindenfeld, J., Mentz, R.. Genitourinary Tract Infections in Patients Taking SGLT2 Inhibitors: JACC Review Topic of the Week. Journal of the American College of Cardiology. 2024;83(16):1568-78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Umanath, K., Testani, J., Lewis, J.. \"Dip\" in eGFR: Stay the Course With SGLT-2 Inhibition. Circulation. 2022;146(6):463-5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Administration TUSFaD. FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. 2018.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Salvatore, T., Galiero, R., Caturano, A., Rinaldi, L., Martino, D.A., Albanese, G., et al.. An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors. International journal of molecular sciences. 2022;23(7).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Xu, B., Kang, B., Li, S., Chen, J., Zhou, J.. Association between sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis of randomized active-controlled trials. International journal of clinical pharmacy. 2025;47(5):1121-31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Pelletier, R., Ng, K., Alkabbani, W., Labib, Y., Mourad, N., Gamble, J.. The association of sodium-glucose cotransporter 2 inhibitors with cancer: An overview of quantitative systematic reviews. Endocrinology, diabetes \u0026amp; metabolism. 2020;3(3):e00145.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"clinical-and-experimental-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"clem","sideBox":"Learn more about [Clinical and Experimental Medicine](https://www.springer.com/journal/10238)","snPcode":"10238","submissionUrl":"https://submission.nature.com/new-submission/10238/3","title":"Clinical and Experimental Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"SGLT2 inhibitors, type 2 diabetes, gastrointestinal neoplasms, meta-analysis, canagliflozin, empagliflozin, dapagliflozin","lastPublishedDoi":"10.21203/rs.3.rs-9272597/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9272597/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe potential carcinogenic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remain controversial, particularly regarding site-specific gastrointestinal (GI) neoplasms. This systematic review and meta-analysis aimed to determine the relationship between SGLT2 inhibitors and the risk of GI neoplasms in patients with T2DM.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMaterials and methods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe searched PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science to March 17, 2025, for RCTs in T2DM comparing SGLT2 inhibitors with placebo or another active comparator. The primary outcome was GI neoplasms; secondary, prespecified site-specific neoplasms (esophageal, gastric, hepatic, pancreatic, colorectal, rectal, biliary). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in Stata 17.0, using fixed- or random-effects models according to the heterogeneity. Prespecified subgroups included agents, dose, exposure duration (\u0026le;\u0026thinsp;52, 52\u0026ndash;104, \u0026gt;\u0026thinsp;104 weeks), age, body mass index (BMI), and hemoglobin A1c (HbA1c). Publication bias was evaluated with funnel plots and Egger\u0026rsquo;s test.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn a pooled analysis of 49 RCTs (n\u0026thinsp;=\u0026thinsp;49,054), SGLT2 inhibitors therapy was not associated with the overall risk of GI neoplasm (OR\u0026thinsp;=\u0026thinsp;1.10, 95% CI: 0.84\u0026ndash;1.44; p\u0026thinsp;=\u0026thinsp;0.46; I\u0026sup2; = 0%). Site-specific analyses were likewise null for esophageal (OR\u0026thinsp;=\u0026thinsp;1.12, 95% CI 0.37\u0026ndash;3.45), gastric (1.20, 0.65\u0026ndash;2.23), hepatic (0.62, 0.31\u0026ndash;1.22), pancreatic (0.93, 0.52\u0026ndash;1.66), colonic (1.28, 0.78\u0026ndash;2.08), colorectal (0.76, 0.27\u0026ndash;2.17), and rectal neoplasms (0.98, 0.49\u0026ndash;1.97), with all p-values\u0026thinsp;\u0026gt;\u0026thinsp;0.05. Subgroup analyses by agents (e.g., canagliflozin, dapagliflozin, empagliflozin), baseline age, BMI, HbA1c, treatment duration, and dose were also non-significant (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Approximately half of the trials had follow-up of one year or less, limiting our ability to evaluate long-term risk.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis comprehensive meta-analysis indicates that SGLT2 inhibitor therapy is not associated with an increased risk of gastrointestinal neoplasms in patients with T2DM across the follow-up durations evaluated, with consistent findings across pharmacologic subclasses.\u003c/p\u003e","manuscriptTitle":"Sodium-Glucose Cotransporter-2 Inhibitors and Gastrointestinal Neoplasm Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 09:37:40","doi":"10.21203/rs.3.rs-9272597/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-04-07T05:31:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-31T06:55:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-31T06:54:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Clinical and Experimental Medicine","date":"2026-03-31T00:26:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"clinical-and-experimental-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"clem","sideBox":"Learn more about [Clinical and Experimental Medicine](https://www.springer.com/journal/10238)","snPcode":"10238","submissionUrl":"https://submission.nature.com/new-submission/10238/3","title":"Clinical and Experimental Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9d003e71-6f7c-4cd4-ae08-3b7fb2c21395","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-14T09:37:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 09:37:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9272597","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9272597","identity":"rs-9272597","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}