Efficacy and safety of SGLT2 inhibitors in patients with diabetic kidney disease: a Bayesian network meta-analysis

Efficacy and safety of SGLT2 inhibitors in patients with diabetic kidney disease: a Bayesian network meta-analysis | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 8 May 2025 V1 Latest version Share on Efficacy and safety of SGLT2 inhibitors in patients with diabetic kidney disease: a Bayesian network meta-analysis Authors : Guo Ma 0000-0001-5524-7172 [email protected] , Zihan Wang , Junwei Chow , Qiuxia Yu , Yu Zhong , Haiyang Liu , Longzhou Li , … Show All … , Yike Wu , Shah Ali , Xinyi Hu , Qiwen Wu , Long Gao , Shan Wang , and Jun Liu Show Fewer Authors Info & Affiliations https://doi.org/10.22541/au.174672745.57116497/v1 264 views 115 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: A Bayesian network meta-analysis (BNMA) was conducted to systematically evaluate efficacy and safety of sodium-glucose co-transporter-2 inhibitors (SGLT2is) in treating DKD. Methods: PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov were searched from inception to Mar 23, 2025. Randomized clinical trials (RCTs) of SGLT2is in treating DKD were included. 17 efficacy and 13 safety outcomes were included, e.g., HbA1c, eGFR, UACR, UTI, GMI. Results: 17 studies with 22,774 participants were included. Among all the included interventions, 10 mg of Dap + 2.5 mg of Sax demonstrated superior efficacy in reducing HbA1c, followed by 25 mg of Emp, 400 mg of Sot, 10 mg of Emp, 20 mg of Bex; 100 mg of Can showed the best efficacy in increasing eGFR, followed by placebo, 20 mg of Bex, 200 mg of Sot, 400 mg of Sot; 300 mg of Can showed the best efficacy in reducing UACR, followed by 25 mg of Emp, 100 mg of Can 10 mg of Dap + 2.5 mg of Sax, 10 mg of Dap; 100 mg of Can showed the lowest incidence of UTI, followed by 5 mg of Dap, 400 mg of Sot, 10 mg of Dap, 5 mg of Ert. Conclusion: SGLT2is displayed favorable efficacy and acceptable safety in treating DKD. 10 mg of Dap + 2.5 mg of Sax demonstrated superior efficacy in reducing HbA1c. 100 mg of Can exhibited the optimal efficacy in improving eGFR and safety. 300 mg of Can showed the best efficacy in reducing UACR. 1. INTRODUCTION Diabetic kidney disease (DKD) is defined as chronic kidney disease (CKD) in individuals with diabetes. 1 DKD is one of the most common complications of diabetes. At present, approximately 537 million adults were suffering from diabetes. 2, 3 Up to 40% of diabetes patients eventually develop to DKD. 2 This means that, approximately 214.8 million adults will suffer from DKD. DKD can progress to end-stage kidney disease (ESKD), 1 cardiovascular disease, even death, 4-6 which seriously threaten human life and health, and lead to a significant global public health concern. Sodium-glucose co-transporter-2 inhibitors (SGLT2is) are novel antidiabetic drugs acting on the SGLT-2 proteins expressed in the proximal convoluted tubules to reduce the reabsorption of filtered glucose, decrease the renal threshold for glucose, and promote urinary glucose excretion. 7-9 They are recommended for the patients with DKD by the guidelines of the American Diabetes Association (ADA) and Kidney Disease:Improving Global Outcomes (KDIGO). 10, 11 However, their efficacy and safety in patients with DKD have not been systematically compared and evaluated up to now. Bayesian network meta-analysis (BNMA) is a statistical method that allows for the simultaneous comparison and ranking of three or more interventions through direct or indirect comparison. Compared to frequency-based network meta-analysis, BNMA provides more accurate estimates and more flexible modeling. 12 Accordingly, we conducted a BNMA to evaluate and compare the efficacy and safety of SGLT2is, e.g., bexagliflozin (Bex), canagliflozin (Can), dapagliflozin (Dap), empagliflozin (Emp), ertugliflozin (Ert), luseogliflozin (Lus) and sotagliflozin (Sot). The study aims to evaluate and compare the efficacy and safety of SGLT2is in treating DKD, which will provide important evidence for optimal choice and rational use of SGLT2is as well as clinical decision-making of DKD medication. 2. METHODS This systematic review and Bayesian network meta-analysis was registered with PROSPERO (CRD42024525370) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. 13 Two researchers (Wang. Z and Chow. J) independently finished the literature search, study selection, quality assessment, and data extraction. Any controversy would be resolved by discussions among all authors. 2.1. Search strategy PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials. gov were systematically searched from their inception up to Mar 23, 2025. RCTs comparing the efficacy and safety of SGLT2is with placebo or other antidiabetic drugs in treating DKD were included. Duplicate records were removed using Endnote X9. The detailed search strategy is shown in Supplementary Table 1. 2.2. Inclusion and exclusion criteria The studies were included in this BNMA if they met all the following eligibility criteria which conformed to the PICOS: (P) Population: the patients with T2DM and DKD, with eGFR ≤60 ml·min -1 ·(1.73 m 2 ) -1 or UACR≥ 30 mg/g, age ≥18 years; (I) Intervention: different daily doses of SGLT2is; (C) Comparisons: placebo or other antidiabetic drugs; (O) Outcomes: including 17 efficacy outcomes and 13 safety outcomes; (S) Study type: RCTs. The following studies were excluded: (1) Patients with type 1 diabetes; (2) Patients without diabetes or CKD; (3) eGFR＞60 ml·min -1 ·(1.73 m 2 ) -1 or UACR＜30 mg/g. Data were extracted from the primary trial reports as well as from secondary data analyses where available. 2.3. Outcome parameters There are 17 efficacy outcomes including changes of glycated hemoglobin A1c (HbA1c), body weight (BW), fasting plasma glucose (FPG), estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), systolic blood pressure (SBP ), diastolic blood pressure (DBP), serum uric acid (SUC), low density lipoprotein (LDL), high density lipoprotein (HDL), percentage of patients achieving HbA1c < 7%, proportion of patients experiencing cardiovascular death (CVD), major adverse cardiovascular events (MACE), hospitalized heart failure (HHF), composite renal outcomes (CRO) and end-stage kidney disease (ESKD) and renal replacement therapy (RRT). There are 13 safety outcomes including proportion of all-cause mortality (ACM), acute kidney injury (AKI), urinary tract infection (UTI), genital mycotic infection (GMI), diarrhea, blood creatinine increased (BCI), hyperkalemia, hypoglycemia, volume depletion (VD), amputation, bone fracture (BF), diabetic ketoacidosis (DKA) and acute pancreatitis (AP). 2.4. Quality assessment Risk of bias of all the included RCTs was evaluated with Cochrane ROB_2, 14 which includes bias in the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. The risk was categorized into three levels: low risk, some concerns and high risk. 2.5. Data extraction Two authors (Zihan Wang, Junwei Chow) independently performed data extraction using a standardized Excel data sheet. The following information of each study was extracted to describe the characteristics of included RCTs: basic information (title, first author, year of publication, study design), participant characteristics (age, sex ratio, disease duration), intervention details (intervention measures and included population of the intervention groups), baseline mean of the measured outcomes and duration of intervention. The outcome with continuous variable (e.g., HbA1c, BW) was pooled with mean differences (MD), and the outcome with discontinuous variable (e.g., safety outcome) was pooled with odd ratio (OR). 2.6. Statistical analysis BNMA was conducted using BUGSnet and GEMTC package of R 4.4.0 (“R & R” of the Statistics Department of the University of Auckland). The random effect model was chosen for analysis. Publication bias was analyzed using Stata 18.0 (Stata Corp, College Station, TX, United States). The results were presented as MD, OR and the surface under the cumulative ranking curve (SUCRA). MD and OR were applied to compare the statistical differences between two intervention groups. SUCRA represents the probability of an intervention being the most effective and safest among all the included interventions, which was used to rank probabilities for different interventions. A higher SUCRA value suggests a higher chance of being considered the best treatment. If an intervention is certain to have the best efficacy or safety, its SUCRA value will be 100%. Heterogeneity levels were detected with the I 2 test. If I 2 > 50 %, the heterogeneity was considered as significant. The deviation information criterion (DIC) was calculated for the outcomes with significant inconsistency. If the difference of DIC between the consistency and inconsistency model were below 5, then the model-fitting degree difference would be considered inconspicuous, and a consistency model would be used for analysis. 15 Two sensitivity analyses were conducted to assess the robustness of the results: (1) only included double-blind RCTs; (2) only included RCTs with intervention duration between 12 weeks and 4 years. 3. RESULTS 3.1. Study selection and characteristics A total of 3094 records were identified from the databases. After removing duplicate records, the titles and abstracts of 610 records were screened, leaving 232 records for full-text review. Ultimately, 17 studies 16-32 involving 22,774 participants were included in the present study (Figure 1). The intervention duration ranged from 12 weeks to 6 years. Specifically, 1 RCTs for 12 weeks, 3 RCTs for 24 weeks, 7 RCTs for 52 weeks, and 6 RCTs for more than 52 weeks. The average HbA1c ranged from 7.3 % to 9.4 % (8.2 ± 1.0 %). Baseline eGFR ranged from 23.8 to 111.17 mL/min/1.73 m 2 (44.9 ± 10.5). Baseline UACR ranged from 64.6 to 2134.0 mg/g (3144.0 ± 2072.2). In one RCT, the interventions were used as an add-on to Sax (Supplementary Table 2). The characteristics of included RCTs and baseline information are shown in Supplementary Table 2 and Supplementary Table 3. 3.2. Efficacy outcomes 3.2.1. HbA1c The BNMA for HbA1c included 17 interventions with 15 active drugs and placebo. The network plot is shown in Figure 2A, and the detailed analysis results for HbA1c are shown in Supplementary Table 5. compared to placebo, 10 mg of Dap + 2.5 mg of Sax, 25 mg of Emp, 400 mg of Sot, and 10 mg of Emp demonstrated superior efficacy in reducing HbA1c (MD [95% CI], -0.60 [-0.92, -0.30] %, -0.38 [-0.56, -0.23] %, -0.37 [-0.50, -0.19] %, -0.36 [-0.57, -0.16] %, respectively). 10 mg of Dap + 2.5 mg of Sax exhibited superior efficacy in reducing HbA1c compared with 15 mg of Ert, 100 mg of Can, 200 mg of Sot, 5 mg of Dap, 5 mg of Ert, 10 mg of Dap and 80 mg of Val (MD [95% CI], -0.42 [-0.80, -0.05], -0.45 [-0.81, -0.08], -0.46 [-0.87, -0.10], -0.49 [-1.05, 0.03], -0.49 [-0.86, -0.12], -0.60 [-0.92, -0.30], -1.07 [-1.84, -0.37] %, respectively). Compared to 200 mg of Sot, 400 mg of Sot exhibited superior efficacy in reducing HbA1c (MD [95% CI], -0.23 [-0.45, -0.01]). According to the SUCRA value, 10 mg of Dap + 2.5 mg of Sax (94.90%) demonstrated the best efficacy in reducing HbA1c, followed by 25 mg of Emp (77.78%), 400 mg of Sot (75.82%), 10 mg of Emp (73.18%), 20 mg of Bex (70.56 %), 300 mg of Can (67.07%), 2.5 mg of Lus (46.83%), 15 mg of Ert (44.86%), 100 mg of Can (39.35%), 200 mg of Sot (36.85%), 5 mg of Dap (36.62%), 5 mg of Ert (35.70%), 10 mg of Dap (33.61%), Placebo (13.61%), and Val (3.26%) (Figure 3A, Supplementary Table 7). 3.2.2. FPG The BNMA for FPG included 11 interventions with 12 active drugs and placebo. The network plot is shown in Figure 2B. The detailed analysis results for FPG are shown in Supplementary Table 5. Compared to placebo, 25 mg of Emp, 400 mg of Sot, 20 mg of Bex, 15 mg of Ert showed significant efficacy in reducing FPG (MD [95% CI], -21.82 [-34.13, -9.70], -15.15 [-28.36, -1.90], -13.72 ([-25.33, -2.36], −11.69 [-21.37, -2.19] mg/dL, respectively). According to the SUCRA values, 25 mg of Emp (89.84%) showed the best efficacy in reducing FPG, followed by 400 mg of Sot (68.06%), 20 mg of Bex (63.99%), 300 mg of Can (61.8%), 200 mg of Sot (57.63%), 15 mg of Ert (51.3%), 5 mg of Dap (49.73%), 100 mg of Can (49.73%), 10 mg of Dap + 2.5 mg of Sax (44.44%), 10 mg of Dap (42.52%), 2.5 mg of Lus (34.53%), 5 mg of Ert (32.98%), and placebo (5.40%) (Figure 3B, Supplementary Table 7). 3.2.3. The proportion of participants with HbA1c< 7% The BNMA for the proportion of participants with HbA1c <7% included 7 interventions with 8 active drugs and placebo. The network plot is shown in Figure 2C. The detailed analysis results for the proportion of participants with HbA1c <7% are shown in Supplementary Table 5. Compared to placebo, 10 mg of Dap + 2.5 mg of Sax showed significantly efficacy in increasing the proportion of participants with HbA1c <7% (OR [95% CI], 6.13 [1.19, 19.83]). The result of SUCRA indicated that 10 mg of Dap + 2.5 mg of Sax (90.91%) showed the best efficacy in increasing the proportion of participants with HbA1c <7%, followed by 400 mg of Sot (63.72%), 20 mg of Bex (55.18%), 5 mg of Ert (52.67%), 200 mg of Sot (52.04%), 25 mg of Emp (44.73%), 10 mg of Dap (41.65%), 15 mg of Ert (36.16%), and placebo (12.95%) (Figure 3C, Supplementary Table 7). 3.2.4. BW The BNMA for BW included 14 interventions with 12 active drugs and placebo. The network plot is shown in Figure 2D. The detailed analysis results for BW are shown in Supplementary Table 5. Compared to placebo, all interventions (except 300 mg of Can) demonstrated significant efficacy in reducing BW. Among them, 10 mg and 5 mg of Dap displayed superior efficacy in reducing BW (MD [95% CI], -1.70 [-2.45, -0.95], -1.66 [-2.79, -0.59] kg), followed by 15 mg of Ert (MD [95% CI], -1.64 [-2.12, -1.19]). The result of SUCRA indicated that 15 mg of Ert (79.07%) showed the best efficacy in reducing BW, followed by 10 mg of Dap (78.10%), 5 mg of Dap (72.02%), 20 mg of Bex (69.78%), 5 mg of Ert (68.29%), 25 mg of Emp (56.69%), 2.5 mg of Lus (50.07%), 400 mg of Sot (39.22%), 300 mg of Can (34.96%), 100 mg of Can (34.75%), 10 mg of Emp (33.51%), 200 mg of Sot (31.57%) and placebo (1.94%) (Figure 3D, Supplementary Table 7). 3.2.5. eGFR The BNMA for eGFR included 16 interventions with 14 active drugs and placebo. The network plot is shown in Figure 2E. The detailed analysis results for eGFR are shown in Supplementary Table 5. 100 mg of Can exhibited superior efficacy in improving eGFR compared with placebo, 200 mg of Sot, 400 mg of Sot, 300 mg of Can, 5 mg of Dap, 5 mg of Ert, 25 mg of Emp, 2.5 mg of Lus, 10 mg of Dap + 2.5 mg of Sax, 15 mg of Ert, 10 mg of Dap (MD [95% CI], 1.71 [0.08, 3.42], 2.48 [0.17, 4.91], 2.86 [0.85, 4.99], 3.05 [0.53, 5.75], 3.14 [0.15, 6.25], 3.92 [0.89, 7.03], 3.94 [1.07, 6.95], 4.21 [1.24, 7.36] 4.59 [1.58, 7.72], 4.81 [1.80, 7.78], 4.89 [2.49, 7.35] mL/min/1.73m 2 , respectively). However, 10 mg of Dap, 15 mg of Ert and 10 mg of Dap + 2.5 mg of Sax demonstrated significant inferior efficacy in improving eGFR compared with placebo (MD [95% CI], -3.19 [-4.92, -1.37], -3.10 [-5.61, -0.58], -2.88 [-5.47, -0.25] mL/min/1.73m 2 , respectively). The result of SUCRA indicated that, among all the included interventions, 100 mg of Can (97.11%) showed the best efficacy in reducing eGFR, followed by placebo (83.51%), 20 mg of Bex (69.98%), 200 mg of Sot (66.76%), 400 mg of Sot (58.68%), 300 mg of Can (54.44%), 5 mg of Dap (53.11%), 80 mg of Val (40.43%), 5 mg of Ert (38.50%), 25 mg of Emp (37.22%), 2.5 mg of Lus (32.61%), 10 mg of Dap + 2.5 mg of Sax (26.41%), 15 mg of Ert (22.22%), 10 mg of Dap (19.04%) (Figure 3E, Supplementary Table 7). 3.2.6. UACR The BNMA for UACR included 8 interventions with 9 active drugs and placebo. The network plot is shown in Figure 2F. The detailed analysis results for UACR are shown in Supplementary Table 5. Compared to placebo, 300 mg of Can exhibited superior efficacy in reducing UACR (MD [95% CI], -483.63 [-904.23, -81.14] mg/g). The result of SUCRA indicated that, among all the included interventions, 300 mg of Can (92.53%) showed the best efficacy in reducing UACR, followed by 25 mg of Emp (68.52%), 100 mg of Can (64.81%), 10 mg of Dap + 2.5 mg of Sax (60.69%), 10 mg of Dap (42.66%), 80 mg of Val (38.13%), 2.5 mg of Lus (31.38%), 5 mg of Dap (28.82%), placebo (22.46%) (Figure 3F, Supplementary Table 7). 3.2.7. HDL The BNMA for HDL included 5 interventions with 7 active drugs and placebo. The network plot is shown in Figure 2G. The detailed analysis results for HDL are shown in Supplementary Table 5. Compared to placebo, all the included interventions showed no significant efficacy in increasing HDL level. The result of SUCRA indicated that, 10 mg of Dap (87.5%) showed the best efficacy in increasing HDL level, followed by 10 mg of Dap + 2.5 mg of Sax (53.45%), 2.5 mg of Lus (53.2%), 100 mg of Can (44.83%), 25 mg of Emp (43.70%), 10 mg of Emp (42.06%), 300 mg of Can (41.82%), placebo (33.42%) (Figure 3G, Supplementary Table 7). 3.2.8. LDL The BNMA for LDL included 5 interventions with 7 active drugs and placebo. The network plot is shown in Figure 2H. The detailed analysis results for LDL are shown in Supplementary Table 5. Compared to placebo, 300 mg and 100 mg of Can showed insignificant efficacy in reducing LDL (MD [95% CI], -5.93 [-144.80, 130.17], -1.06 [-138.31, 134.46] mg/dL). However, 10 mg of Dap insignificantly increased LDL level (MD [95% CI], 186.54 [-299.49, 654.05] mg/dL). The result of SUCRA indicated that 300 mg of Can (67.85%) showed the best efficacy in reducing LDL level, followed by 100 mg of Can (55.56%), 10 mg of Dap + 2.5 mg of Sax (54.21%), placebo (54.00%), 25 mg of Emp (52.00%), 10 mg of Emp (48.19%), and so on (Figure 3H, Supplementary Table 7). 3.2.9. SBP The BNMA for SBP included 16 interventions with 13 active drugs and placebo. The network plot is shown in Figure 2I. The detailed analysis results for SBP are shown in Supplementary Table 5. 10 mg of Dap + 2.5 mg of Sax, 10 mg of Emp, 25 mg of Emp, 10 mg of Dap, 15 mg of Ert, 100 mg of Can, and 5 mg of Ert showed the superior efficacy in reducing SBP compared with placebo (MD [95% CI], -4.93 [-9.26, -0.65], -4.86 [-7.44, -2.26], -4.42 [-6.50, -2.29], -4.11 [-6.99, -1.31], -3.30 [-5.58, -1.11], -2.77 [-4.14, -1.56], -2.41 [-4.57, -0.16] mmHg, respectively). The result of SUCRA indicated that 10 mg of Emp (81.86%) showed the best efficacy in reducing SBP, follow by 10 mg of Dap + 2.5 mg of Sax (77.24%), 25 mg of Emp (76.44%), 10 mg of Dap (70.04%), 15 mg of Ert (58.25%), 5 mg of Dap (53.25%), 100 mg of Can (47.69%), 2.5 mg of Lus (46.02%), 20 mg of Bex (45.53%), 5 mg of Ert (40.13%), 200 mg of Sot (37.6%), 400 mg of Sot (32.75%), 300 mg of Can (28.81%), and placebo (4.47%) (Figure 3I, Supplementary Table 7). 3.2.10. DBP The BNMA for DBP included 8 interventions with 7 active drugs and placebo. The network plot is shown in Figure 2J. The detailed analysis results for DBP are shown in Supplementary Table 5. Compared to placebo, no intervention significantly decreased DBP. The result of SUCRA indicated that 25 mg of Emp (76.1%) showed the best efficacy in decreasing DBP (80.61%), followed by 300 mg of Can (57.32%), 10 mg of Dap (53.09%), 400 mg of Sot (52.74%), 100 mg of Can (52.67%), 5 mg of Dap (40.61%), and 2.5 mg of Lus (35.65%), and placebo (31.8%) (Figure 3J, Supplementary Table 7). 3.2.11. MACE The BNMA for MACE included 7 interventions with 5 active drugs and placebo. The network plot is shown in Figure 2K. The detailed analysis results for MACE are shown in Supplementary Table 5. Compared to placebo, 400 mg and 200 mg of Sot insignificantly decreased incidence of MACE (OR [95% CI], 0.86 [0.18, 2.58], 0.60 [0.07, 2.08]). Compared to 20 mg of Bex, all the included interventions significantly decreased incidence of MACE (Supplementary Table 5). The result of SUCRA indicated that 200 mg of Sot (82.95%) exhibited the best efficacy in reducing incidence of MACE, followed by 400 mg of Sot (64.55%), 100 mg of Can (55.10%), Emp with flexible dose (53.74%), placebo (42.74%) and 20 mg of Bex (0.94%) (Figure 3K, Supplementary Table 7). 3.2.12. CVD The BNMA for CVD included 6 interventions with 4 active drugs and placebo. The network plot is shown in Figure 2L. The detailed analysis results for CVD are shown in Supplementary Table 5. Compared to all the other included interventions, 200 mg of Sot significantly decreased incidence of CVD (Supplementary Table 5). The result of SUCRA indicated that 200 mg of Sot (99.67%) showed the best efficacy in decreasing incidence of CVD, followed by Emp with flexible dose (45.05%), 400 mg of Sot (42.03%), 100 mg of Can (32.94%) and placebo (30.31%) (Figure 3L, Supplementary Table 7). 3.2.13. HHF The BNMA for HHF included 6 interventions with 4 active drugs and placebo. The network plot is shown in Figure 2M. The detailed analysis results for HHF are shown in Supplementary Table 5. Compared to placebo, 400 mg of Sot and Emp with flexible dose, 200 mg of Sot insignificantly reduced the incidence of HHF (OR [95% CI], 0.43 [0.03, 1.70], 0.62 [0.04, 2.41], 0.96 [0.03, 4.31], respectively). The result of SUCRA indicated that 200 mg of Sot (81.92%) showed the best efficacy in reducing incidence of HHF, followed by 100 mg of Can (60.08%), Emp with flexible dose (51.80%), 400 mg of Sot (43.02%) and placebo (13.17%) (Figure 3M, Supplementary Table 7). 3.2.14. CRO The BNMA for CRO included 6 interventions with 4 active drugs and placebo. The network plot is shown in Figure 2N. The detailed analysis results for CRO are shown in Supplementary Table 5. Compared to placebo, Emp with flexible dose insignificantly decreased incidence of CRO (OR [95% CI], 0.30 [0.02, 1.16]). The result of SUCRA indicated that Emp with flexible dose (91.43%) showed the best efficacy in decreasing incidence of CRO, followed by 100 mg of Can (67.61%), 400 mg of Sot (45.78%), placebo (23.27%), and 200 mg of Sot (21.88%) (Figure 3N, Supplementary Table 7). 3.2.15. ESKD The BNMA for ESKD events included 3 interventions with 3 active drugs and placebo. The network plot is shown in Figure 2O. The detailed analysis results for ESKD shown in Supplementary Table 5. Compared to placebo and 200 mg of Sot, 100 mg of Can insignificantly decrease incidence of ESKD (OR [95% CI], 0.76 (0.14, 2.49], 0.96 (0.07, 4.84]). The result of SUCRA indicated that 100 mg of Can (76.12%) showed the best efficacy in decreasing incidence of ESKD, followed by 400 mg of Sot (52.4%), placebo (40.1%), and 200 mg of Sot (31.39%) (Figure 3O, Supplementary Table 7). 3.2.16. RRT The BNMA for RRT included 3 interventions with 5 active drugs and placebo. The network plot is shown in Figure 2P. The detailed analysis results for RRT are shown in Supplementary Table 5. Compared to placebo, 10 mg and 5 mg of Dap, 100 mg of Can insignificantly decreased incidence of RRT (OR [95% CI], 0.59 [0.01, 3.13], 0.60 [0.01, 3.09], 0.86 [0.24, 2.30], respectively). The result of SUCRA indicated that 10 mg of Dap (60.57%) showed the best efficacy in decreasing incidence of RRT, followed by 400 mg of Sot (59.94%), 5 mg of Dap (59.06%), 200 mg of Sot (55.44%), 100 mg of Can (39.67%), and placebo (25.34%) (Figure 3P, Supplementary Table 7). 3.2.17. SUC The BNMA for included 7 interventions with 10 active drugs and placebo. The network plot is shown in Figure 2Q. The detailed analysis results for SUC are shown in Supplementary Table 5. Compared to 10 mg of Dap and 80 mg of Val, 5mg of Dap showed superior efficacy in reducing SUC (MD [95% CI], -58.85 [-115.36 to -1.67] μmol/L, -87.94 [-169.23, 5.73] μmol/L, respectively). The result of SUCRA indicated that 5 mg of Dap (91.67%) showed the best efficacy in reducing SUC, followed by 10 mg of Dap + 2.5 mg of Sax (75.57%), 10 mg of Emp (65.85%), 25 mg of Emp (55.22%), 400 mg of Sot (50.92%), 200 mg of Sot (46.99%), 2.5 mg of Lus (43.51%), placebo (32.88%), 10 mg of Dap (28.70%), and 80 mg of Val (8.68%) (Figure 3Q, Supplementary Table 7). 3.3 Safety outcomes 3.3.1. ACM The BNMA for ACM included 15 interventions with 13 active drugs and placebo. The network plot is shown in Figure 2R. The detailed analysis results for ACM are shown in Supplementary Table 5. 300 mg of Can significantly decreased incidence of ACM compared with all the other included interventions except 20 mg of Bex (Supplementary Table 5). The result of SUCRA indicated that 300 mg of Can (98.17%) showed the lowest incidence of ACM, followed by 20 mg of Bex (72.00%), 5 mg of Dap (66.99%), 200 mg of Sot (64.32%), Emp with flexible dose (52.28%), 10 mg of Dap (51.23%), 25 mg of Emp (46.98%), 400 mg of Sot (46.31%), placebo (44.81%), 100 mg of Can (41.55%), 15 mg of Ert (40.41%), 10 mg of Dap + 2.5 mg of Sax (35.42%), 5 mg of Ert (35.25%), and 2.5 mg of Lus (4.28%) (Figure 3R, Supplementary Table 7). 3.3.2. UTI The BNMA for UTI included 16 interventions with 15 active drugs and placebo. The network plot is shown in Figure 2S. The detailed analysis results for UTI are shown in Supplementary Table 5. Compared to placebo, 2.5 mg of Lus and 80 mg of Val significantly increased the incidence of UTI (OR [95% CI], 3.59E+14 [2.45, 1.02E+14], 8.06E+17 [2.47, 1.68E+18], respectively). The result of SUCRA indicated that 100 mg of Can (89.03%) showed the lowest incidence of UTI, followed by 5 mg of Dap (66.83%), 400 mg of Sot (66.45%), 10 mg of Dap (66.14%), 5 mg of Ert (66.03%), placebo (61.92%), 15 mg of Ert (61.56%), 25 mg of Emp (58.34%), Emp with flexible dose (55.38%), 200 mg of Sot (45.78%), 10 mg of Dap + 2.5 mg of Sax (42.06%), 300 mg of Can (35.75%), 20 mg of Bex (25.34%), 2.5 mg of Lus (4.88%), and 80 mg of Val (4.49%) (Figure 3S, Supplementary Table 7). 3.3.3. GMI The BNMA for GMI included 15 interventions with 13 active drugs and placebo. The network plot is shown in Figure 2T. The detailed analysis results for GMI are shown in Supplementary Table 5. Compared to all the other included interventions, 20 mg of Bex showed the highest incidence of GMI (Supplementary Table 5). The result of SUCRA indicated that 100 mg of Can (83.22%) showed the lowest incidence of GMI, followed by placebo (82.61%), 300 mg of Can (82.52%), 400 mg of Sot (56.12%), 25 mg of Emp with flexible dose (54.45%), 10 mg of Dap (49.31%), 5 mg of Dap (49.09%), 200 mg of Sot (48.81%), 15 mg of Ert (46.88%), 10 mg of Dap + 2.5 of Sax (40.88%), 5 mg of Ert (39.61%), 2.5 mg of Lus (11.86%), 20 mg of Bex (3.96%) (Figure 3T, Supplementary Table 7). 3.3.4. DKA The BNMA for DKA included 7 interventions with 6 active drugs and placebo. The network plot is shown in Figure 2U. The detailed analysis results for DKA are shown in Supplementary Table 5. Compared to placebo, all the included interventions showed insignificant higher incidence of DKA (Supplementary Table 5). Compared to 10 mg of Dap, 10 mg of Dap + 2.5 mg of Sax significantly decreased incidence of DKA (OR [95% CI], 0.16 [0.00, 0.13]). The result of SUCRA indicated that 10 mg of Dap + 2.5 mg of Sax (80.23%) showed the lowest incidence of DKA, followed by 200 mg of Sot (63.71%), placebo (62.53%), Emp with flexible dose (53.98%), 400 mg of Sot (46.10%), 100 mg of Can (34.68%), and 10 mg of Dap (8.77%) (Figure 3U, Supplementary Table 7). 3.3.5. Hypoglycemia The BNMA for hypoglycemia included 15 interventions with 14 active drugs and placebo. The network plot is shown in Figure 2V. The detailed analysis results for hypoglycemia are shown in Supplementary Table 5. Compared to 10 mg of Dap + 2.5 mg of Sax, both Emp with flexible dose and 10 mg of Dap significantly decreased incidence of hypoglycemia (OR [95% CI], 0.52 [0.25, 0.97], 0.60 [0.34, 1.00]). Compared to 80 mg of Val, Emp with flexible dose, 5 mg of Dap, and 10 mg of Dap significantly decreased incidence of hypoglycemia (OR [95% CI], 0.08 [0.00, 0.93], 0.09 [0.00, 0.87], 0.09 [0.00, 0.99], respectively). The result of SUCRA indicated that Emp with flexible dose (80.26%) showed the lowest incidence of hypoglycemia, followed by 2.5 mg of Lus (78.37%), 5 mg of Dap (64.30%), 15 mg of Ert (64.24%), 400 mg of Sot (61.93%), 10 mg of Dap (60.92%), 25 mg of Emp (52.92%), 100 mg of Can (50.68%), 20 mg of Bex (48.87%), placebo (47.80%), 5 mg of Ert (41.28%), 200 mg of Sot (30.30%), 10 mg of Dap + 2.5 mg of Sax (15.05%) and 80 mg of Val (3.10%) (Figure 3V, Supplementary Table 7). 3.3.6. VD The BNMA for VD included 8 interventions with 9 active drugs and placebo. The network plot is shown in Figure 2W. The detailed analysis results for VD are shown in Supplementary Table 5. Compared to all the other included interventions, 2.5 mg of Lus significantly decreased the incidence of VD (Supplementary Table 5). The result of SUCRA indicated that 2.5 mg of Lus (99.55%) showed the lowest incidence of VD, followed by 100 mg of Can (68.78%), Emp with flexible dose (55.48%), 15 mg of Ert (52.00%), placebo (48.32%), 10 mg of Dap (47.59%), 5 mg of Ert (43.36%), 400 mg of Sot (37.91%), 10 mg of Dap + 2.5 mg of Sax (23.72%), and 200 mg of Sot (23.30%) (Figure 3W, Supplementary Table 7). 3.3.7. BF The BNMA for BF included 11 interventions with 9 active drugs and placebo. The network plot is shown in Figure 2X. The detailed analysis results for BF are shown in Supplementary Table 5. Compared to 5 mg and 10 mg of Dap, 10 mg of Dap + 2.5 mg of Sax significantly decreased incidence of BF (OR [95% CI], 0.08 [0.00 to 0.17], 0.04 [0.00 to 0.14], respectively). The result of SUCRA indicated that 10 mg of Dap + 2.5 mg of Sax (97.54%) showed the lowest risk for BF, followed by 200 mg of Sot (77.65%), 100 mg of Can (57.94%), 400 mg of Sot (57.07%), Emp with flexible dose (52.03%), placebo (46.61%), 20 mg of Bex (44.22%), 25 mg of Emp (38.17%), 5 mg of Dap (15.8%), and 10 mg of Dap (12.98%) (Figure 3X, Supplementary Table 7). 3.3.8. Amputation The BNMA for amputation included 8 interventions with 6 active drugs and placebo. The network plot is shown in Figure 2Y. The detailed analysis results for amputation are shown in Supplementary Table 5. Compared to 200 mg of Sot, 400 mg of Sot insignificantly decreased incidence of amputation (OR [95% CI],0.80 [0.02, 3.87]). Compared to placebo, all the included insignificantly increased incidence of amputation (Supplementary Table 5). The result of SUCRA indicated that 400 mg of Sot (81.02%) showed the lowest incidence of amputation, followed by placebo (76.64%), 100 mg of Can (73.39%), 200 mg of Sot (59.61%), 20 mg of Bex (20.76%), 10 mg of Dap + 2.5 mg of Sax (19.8%), 10 mg of Dap (18.77%) (Figure 3Y, Supplementary Table 7). 3.3.9. AKI The BNMA for AKI included 4 interventions with 5 active drugs and placebo. The network plot is shown in Figure 2Z. The detailed analysis results for AKI are shown in Supplementary Table 5. Compared to Emp with flexible dose, the other included interventions insignificantly increased incidence of AKI (Supplementary Table 5). The result of SUCRA indicated that Emp with flexible dose (79.69%) showed the lowest incidence of AKI, followed by 5 mg of Ert (71.63%), 100 mg of Can (51.26%), 15 mg of Ert (37.58%), placebo (34.63%), 20 mg of Bex (25.20%) (Figure 3Z, Supplementary Table 7). 3.3.10. BCI The BNMA for BCI included 3 interventions with 4 active drugs and placebo. The network plot is shown in Figure 2AA. The detailed analysis results for BCI are shown in Supplementary Table 5. 10 mg of Dap + 2.5 mg of Sax, and 10 mg of Dap, 2.5 mg of Lus significantly decreased incidence of BCI compared with placebo (OR [95% CI], 0.06 [0.00, 0.12], 0.02 [0.00, 0.02], 0.47 [0.00, 0.21], respectively). The result of SUCRA indicated that 2.5 mg of Lus (87.58%) showed the lowest incidence of BCI, followed by 5 mg of Dap (86.80%) and 10 mg of Dap (36.30%), placebo (34.69%), 10 mg of Dap + 2.5 mg of Sax (4.62%) (Figure 3AA, Supplementary Table 7). 3.3.11. Diarrhea The BNMA for diarrhea included 4 interventions with 3 active drugs and placebo. The network plot is shown in Figure 2AB. The detailed analysis results for diarrhea are shown in Supplementary Table 5. Compared to placebo, 400 mg of Sot significantly increased incidence of diarrhea (OR [95% CI], 1.53 [1.02, 2.3]). The result of SUCRA indicated that 25 mg of Emp (78.19%) showed the lowest incidence of diarrhea, followed by placebo (66.47%), 200 mg of Sot (37.66%) and 400 mg of Sot (17.69%) (Figure 3AB, Supplementary Table 7). 3.3.12. Hyperkalemia The BNMA for hyperkalemia included 4 interventions with 5 active drugs and placebo. The network plot is shown in Figure 2AC. The detailed analysis results for hyperkalemia are shown in Supplementary Table 5. Compared to Emp with flexible dose, the other included interventions showed insignificant higher incidence of hyperkalemia (Supplementary Table 5). The result of SUCRA indicated that Emp with flexible dose (75.33%) showed the lowest incidence of hyperkalemia, followed by 10 mg of Dap (70.35%), 5 mg of Dap (51.83%), and 100 mg of Can (47.78%), placebo (27.66%), and 25 mg of Emp (27.07%) (Figure 3AC, Supplementary Table 7). 3.3.13. AP The BNMA for AP included 3 interventions with 2 active drugs and placebo. The network plot is shown in Figure 2AD. The detailed analysis results for AP are shown in Supplementary Table 5. Compared to placebo and 100 mg of Can, 400 mg of Sot showed insignificant lower incidence of AP (OR [95% CI], 0.78 [0.13 to 2.61], 0.36 [0.01 to 1.82], respectively). The result of SUCRA indicated that 400 mg of Sot (86.62%) showed the lowest incidence of AP, followed by placebo (55.48%), and 100 mg of Can (7.90%) (Figure 3AD, Supplementary Table 7). 3.4. Risk of bias Risk of bias of included studies is shown in Figure 4. Overall, among the included 17 RCTs, 15 studies were identified as low risks of bias, and two studies 23,27 were deemed as high risk. 3.5. Heterogeneity and inconsistency The model fitting and heterogeneity testing results are shown in Supplementary Figure 1 and Supplementary Table 4. Heterogeneity levels were detected with I 2 test. If I 2 > 50%, the heterogeneity was considered as significant (Supplementary Table 4). The difference values of DIC between inconsistency and consistency models in all outcomes were less than five (Supplementary Figure 1), therefore, random effect and consistency models were applied. 3.6. Publication bias Publication bias, caused by unpublished or undetected studies, was shown using a funnel plot. If the dots (representing the included RCTs) are symmetrically distributed around the line of combined effect size (the intermediate vertical line of the funnel) in the funnel plot, the publication bias will be considered non-significant. 33 The comparison-adjusted funnel plots and all included intervention for funnel plots are shown in Figure 5 and Supplementary Table 8. For ACM, UTI and diarrhea, the dots were not symmetrically distributed about the size line of the combined effect, suggesting there was a certain degree of publication bias for these three outcomes. However, there were fewer than ten studies included for diarrhea outcomes, so its publication bias assessment might not be reliable. 34-36 3.7. Sensitivity analysis The sensitivity analysis results for most interventions were consistent with the main analysis. In the sensitivity analysis of double-blind RCTs, significant changes were observed in DBP for 100 mg of Can. In the sensitivity analysis of studies with 12 week-4 years of treatment, significant changes were observed in FPG for 20 mg of Bex, 10 mg of Dap, 15 mg of Ert, and 400 mg of Sot, eGFR for 5 and 15 mg of Ert, 200 mg of Sot, DBP for 100 mg of Can and SBP for 5 mg of Ert. Overall, the results are robust (Supplementary Table 6). 4. DISCUSSION This BNMA included 17 studies with 22,774 patients comprehensively assessed the efficacy and safety of SGLT2is in the treatment of DKD, which involved in 17 efficacy outcomes and 13 safety outcomes. SGLT2is displayed favorable efficacy in protecting the kidneys, lowering blood sugar, regulating blood lipids, and lowering blood pressure. In terms of the kidney protection, 100 mg of Can exhibited the optimal efficacy in increasing eGFR levels, and 300 mg of Can demonstrated the optimal efficacy in decreasing UACR levels. In terms of glucose-lowering efficacy, the combination of 10 mg of Dap + 2.5 mg of Sax exhibited the optimal efficacy in reducing HbA1c level and increasing the proportion of participants with HbA1c< 7%. 25 mg of Emp demonstrated the optimal efficacy in reducing FPG. In addition, 400 mg of Sot exhibited good efficacy in reducing HbA1c and FPG, and increasing the proportion of participants with HbA1c< 7%, which ranked in the top three among all the included interventions. In terms of lipid improvement, 10 mg of Dap exhibited the optimal efficacy in increasing HDL level but lacked an advantage in lowering LDL level. 300 mg and 100 mg of Can exhibited the optimal efficacy in lowering LDL levels but lacked an advantage in increasing HDL levels. In terms of blood pressure-lowering efficacy, 10 mg of Emp exhibited the optimal efficacy in lowing SBP. Significant efficacy of SGLT2is in lowering blood sugar, regulating blood lipids and lowering blood pressure contribute to improve renal function in DKD patients. SGLT2is also displayed favorable cardio-renal benefit. 200 mg of Sot exhibited the optimal efficacy in reducing incidence of CVD, MACE, and HHF. 100 mg of Can demonstrated the optimal efficacy in reducing incidence of CRO and ESKD, and 200 mg of Sot exhibited the optimal efficacy in reducing incidence of RRT. This BNMA results is consistent with ADA and KDIGO guidelines in which SGLT2is are recommended for cardiovascular events reduction and renal protection. 10, 11 Especially, some large-scale RCTs 37-41 had been shown that SGLT2is protect renal function independent of glycemic control. This means that SGLT2is are not only suitable for DKD patients, but also for CKD patients without T2DM. Thus, it can be seen that, SGLT2is exhibited multiple therapeutic effects such as lowering blood glucose, weight loss, regulating blood lipids, lowering blood pressure, cardiac and renal benefits. Among the included SGLT2is, 100 mg of Can is particularly suitable for DKD patients with elevated lipids and cardio-renal dysfunction, 300 mg of Can is particularly suitable for DKD patients with elevated lipids and/or hypertension, 25 mg of Emp is particularly suitable for DKD patients with moderate-to-severe proteinuria and/or hypertension, 200 mg of Sot is particularly suitable for DKD patients with cardiovascular disease, and 10 mg of Dap + 2.5 mg of Sax is particularly suitable for DKD patients with elevated lipids. On the whole, SGLT2is exhibited acceptable safety in the treatment of DKD. Among the included SGLT2is, 100 mg of Can exhibited the optimal effect in decreasing the incidence of UTI and GMI, and 300 mg of Can displayed the optimal effect in decreasing incidence of ACM. 10 mg of Dap + 2.5 mg of Sax displayed the optimal effect in decreasing incidence of DKA and BF. 4.1. Limitations Several limitations of this study need to be acknowledged. First, the implementation of subgroup analysis was precluded by insufficient sample size among included RCT, which hindered the evaluation and comparison of efficacy and safety in patients with progressive DKD. Second, some of the included studies involved patients from specific countries or regions, which may limit the generalizability of our findings to broader DKD populations. Third, not all the included RCTs provided the above 30 efficacy and safety outcome measures in this study. For example, only the data in three publications were reported for AP, suggesting that more RCTs with more outcome measures are needed to be included so as to draw reliable conclusions. 5. CONCLUSION In conclusion, the included SGLT2is displayed favorable efficacy and acceptable safety in the treatment of DKD. Of them, 10 mg of Dap + 2.5 mg of Sax displayed the optimal efficacy in reducing HbA1c and increasing the proportion of participants with HbA1c<7% and as well as safety in decreasing incidence of DKA and BF; 100 mg of Can exhibited the optimal efficacy in increasing eGFR and safety in decreasing incidence of UTI and GMI; 300 mg of Can demonstrated the optimal efficacy in decreasing UACR and safety in decreasing incidence of ACM. ARTICLE INFORMATION CRediT contributions ZW : Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Writing - Original Draft, Writing - Review & Editing, Visualization, Project administration. JC : Methodology, Validation, Formal analysis, Investigation, Visualization, Writing - Review & Editing; QY : Methodology, Validation, Formal analysis, Writing – Review & Editing; YZ , Methodology, Validation, Formal analysis, Writing – Review & Editing; HL , Methodology, Validation, Formal analysis, Writing – Review & Editing; LL , Methodology, Validation, Formal analysis, Writing – Review & Editing; YW , Methodology, Validation, Formal analysis, Writing – Review & Editing; AA , Methodology, Validation, Formal analysis, Writing – Review & Editing; XH , Methodology, Validation, Formal analysis, Writing – Review & Editing; QW , Methodology, Validation, Formal analysis, Writing – Review & Editing; LG , Methodology, Validation, Formal analysis, Writing – Review & Editing; SW , Methodology, Validation, Formal analysis, Writing – Review & Editing; JL : Conceptualization, Methodology, Validation, Formal analysis, Project administration, Supervision. GM : Conceptualization, Methodology, Validation, Formal analysis, Writing - Review & Editing, Project administration, Supervision. GM is the guarantor. Declaration of Competing Interest The authors declare no conflict of interest. Data availability The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. Funding This work was supported by the National Natural Science Funds of China [Grants 82074109, 81873078, 81374051, 81773687 and 82270852] and Shanghai Municipal Key Discipline (2024ZDXK0016) Reference 1. Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers . 2015;1:15018. 2. International Diabetes Federation. Diabetes and kidney disease | IDF Diabetes Atlas . . Accessed April 13, 2025. 3. Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol . 2017;12(12):2032-2045. 4. 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Figures legend FIGURE 1 Study flow diagram of the study selection process. n , number of records. PICOS, referred to Population (P), Intervention (I), Comparison(C), Outcomes (O) and Study (S) criteria. FIGURE 2 Network plot comparing included interventions for outcomes. The line width was proportional to the number of studies comparing each pair of treatments. The wider line indicated that more studies were included in this comparison. The size of each node was proportional to the number of participants (sample size). The larger node indicated more participants in the corresponding intervention group. BEX20, bexagliflozin 20mg; CAN100, canagliflozin 100mg; CAN300, canagliflozin 300mg; DAP10, dapagliflozin 10mg; DAP5, dapagliflozin 5mg; DAP10_SAX2.5, dapagliflozin 10mg + saxagliptin 2.5mg; ERT5, ertugliflozin 5mg; ERT15, ertugliflozin 15mg; EMP10: empagliflozin 10mg; EMP25, empagliflozin 25 mg; Emp, empagliflozin with flexible dose; LUS2.5, luseogliflozin 2.5mg; PLA, placebo; SOT400, sotagliflozin 400mg; SOT200, sotagliflozin 200mg; Val80, valsartan 80mg. A, HbA1c; B, FPG; C, HbA1c<7%; D, BW; E, eGFR; F, UACR; G, HDL; H, LDL; I, SBP; J, DBP; K, MACE; L, CVD; M, HHF; N, CRO; O, ESKD; P, RRT; Q, SUC; R, ACM; S, UTI; T, GMI; U, DKA; V, Hypoglycemia; W, VD; X, BF; Y, Amputation; Z, AKI; AA, BCI; AB, Diarrhea; AC, Hyperkalemia; AD, AP. FIGURE 3 Plot of the SUCRA of outcomes. Different colors represented different interventions. The interventions with higher SUCRA values had better efficacy or safety. SUCRA values for all outcomes are shown in Supplementary Table 7. SUCRA, surface under the cumulative ranking curve. BEX20, bexagliflozin 20mg; CAN100, canagliflozin 100mg; CAN300, canagliflozin 300mg; DAP10, dapagliflozin 10mg; DAP5, dapagliflozin 5mg; DAP10_SAX2.5, dapagliflozin 10mg + saxagliptin 2.5mg; ERT5, ertugliflozin 5mg; ERT15, ertugliflozin 15mg; EMP10: empagliflozin 10mg; EMP25, empagliflozin 25 mg; Emp, empagliflozin with flexible dose; LUS2.5, luseogliflozin 2.5mg; PLA, placebo; SOT400, sotagliflozin 400mg; SOT200, sotagliflozin 200mg; Val80, valsartan 80mg. A, HbA1c; B, FPG; C, HbA1c<7%; D, BW; E, eGFR; F, UACR; G, HDL; H, LDL; I, SBP; J, DBP; K, MACE; L, CVD; M, HHF; N, CRO; O, ESKD; P, RRT; Q, SUC; R, ACM; S, UTI; T, GMI; U, DKA; V, Hypoglycemia; W, VD; X, BF; Y, Amputation; Z, AKI; AA, BCI; AB, Diarrhea; AC, Hyperkalemia; AD, AP. FIGURE 4 Assessment of risk of bias of included studies. FIGURE 5 Funnel plot of outcomes. The scattered dots in the plot represent the different studies included (RCTs). The perpendicular bisector (the red line) of the funnel represented the combined effect size. The two oblique dashed lines comprising the funnel represented the 95% confidence interval. A, HbA1c; B, FPG; C, HbA1c<7%; D, BW; E, eGFR; F, UACR; G, HDL; H, LDL; I, SBP; J, DBP; K, MACE; L, CVD; M, HHF; N, CRO; O, ESKD; P, RRT; Q, SUC; R, ACM; S, UTI; T, GMI; U, DKA; V, Hypoglycemia; W, VD; X, BF; Y, Amputation; Z, AKI; AA, BCI; AB, Diarrhea; AC, Hyperkalemia; AD, AP. FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 Supplementary Material File (fig. 2 a-j.tif) Download 36.34 MB File (fig. 2 k-t.tif) Download 35.80 MB File (fig. 2 u-ad.tif) Download 35.69 MB File (fig. 3 a-j.tif) Download 37.87 MB File (fig. 3 k-t.tif) Download 37.24 MB File (fig. 3 u-ad.tif) Download 36.92 MB File (fig. 5 a-j.tif) Download 36.45 MB File (fig. 5 k-t.tif) Download 36.29 MB File (fig. 5 u-ad.tif) Download 36.21 MB File (graphical abstract.tif) Download 25.95 MB File (supplementary fig.1 a-p.tif) Download 36.19 MB File (supplementary fig.1 q-ad.tif) Download 35.97 MB Information & Authors Information Version history V1 Version 1 08 May 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords diabetes endocrine pharmacology endocrine disrupters Authors Affiliations Guo Ma 0000-0001-5524-7172 [email protected] Fudan University View all articles by this author Zihan Wang Fudan University View all articles by this author Junwei Chow Fudan University View all articles by this author Qiuxia Yu Fudan University View all articles by this author Yu Zhong Fudan University View all articles by this author Haiyang Liu Fudan University View all articles by this author Longzhou Li Fudan University View all articles by this author Yike Wu Fudan University View all articles by this author Shah Ali Fudan University View all articles by this author Xinyi Hu Fudan University View all articles by this author Qiwen Wu Fudan University View all articles by this author Long Gao Fudan University View all articles by this author Shan Wang Fudan University View all articles by this author Jun Liu Shanghai Fifth People's Hospital View all articles by this author Metrics & Citations Metrics Article Usage 264 views 115 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Guo Ma, Zihan Wang, Junwei Chow, et al. Efficacy and safety of SGLT2 inhibitors in patients with diabetic kidney disease: a Bayesian network meta-analysis. Authorea . 08 May 2025. DOI: https://doi.org/10.22541/au.174672745.57116497/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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