Oral antidiabetic therapy versus early insulinization on glycemic control in newly diagnosed type 2 diabetes patients: a retrospective matched cohort study

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Methods A retrospective cohort study conducted at a medical center in Taiwan analyzed 1,256 eligible patients from January 2007 to December 2017. Propensity score matching resulted in well-balanced groups of 113 patients each in the oral antidiabetic drug (OAD) and early insulinization cohorts. Glycemic outcomes were assessed in both groups. Results Patients exclusively using OAD showed consistently lower glycated hemoglobin (HbA1c) levels at 3, 12, 24, and 36 months compared to insulin users. At later periods, 78.8% of OAD users achieved glycemic control versus 67.3% of insulin users, with a marginally significant difference. Subgroup analyses suggested a trend favoring well-controlled diabetes in the OAD group, though not statistically significant. Conclusions Our study finds oral antidiabetic therapy is not inferior to early insulinization for glycemic control in newly diagnosed type 2 diabetes patients, irrespective of initial HbA1c levels. This supports oral therapy as a rational treatment option, even in cases with elevated HbA1c at diagnosis. Figures Figure 1 Figure 2 Figure 3 Introduction Diabetes stands as a growing global pandemic characterized by escalating prevalence rates and enduring chronic complications associated with hyperglycemia. Complications include retinopathy, neuropathy, nephropathy, and cardiovascular disease, imposing significant socioeconomic burdens ( 1 – 3 ). The United Kingdom Prospective Diabetes Study (UKPDS) and the Diabetes Control and Complications Trial (DCCT) highlighted "metabolic memory," revealing that early glycemic control in diabetes offers lasting end-organ protection, independent of subsequent treatment or control quality ( 4 – 7 ). This emphasizes the vital need for timely and optimal glycemic control to prevent diabetes-related complications. Intensive short-term insulin therapy has been shown to induce glycemic remission in severe, newly diagnosed type 2 diabetes patients ( 8 – 10 ). Despite the availability of oral antidiabetic drugs (OADs), insulin remains the most potent treatment, providing established benefits including mitigating glucotoxicity, suppressing lipotoxicity, dampening inflammation, abolishing reactive oxygen species (ROS), fostering β-cell recovery, preserving functionality, and bolstering insulin sensitivity ( 11 – 22 ). However, challenges and barriers associated with insulin therapy, including the risk of hypoglycemia, weight gain, injection anxieties, and logistical inconveniences, may discourage its initiation. Type 2 diabetes is a complex metabolic disorder marked by heightened insulin resistance and diminished β-cell function, exhibiting multifaceted and diverse characteristics ( 12 – 14 ). It is influenced by a multitude of risk factors, including sedentary lifestyle, dietary habits, obesity, aging, familial predisposition, and ethnic background ( 1 , 15 – 18 ). DeFronzo proposed prioritizing the reversal of established pathogenic abnormalities in type 2 diabetes by combining multiple drugs ( 23 ). Since 2000, various OADs targeting diverse mechanisms have been developed. Thus, for newly diagnosed type 2 diabetes patients, OADs alone may be comparable to early insulinization, before the onset of β-cell failure. Our real-world study aims to compare oral antidiabetic therapy versus early insulinization for glycemic control in these patients. Methods Subjects . This retrospective cohort study was conducted at the Changhua Christian Hospital (CCH), Taiwan. A total of 23629 patients with type 2 diabetes were screened for eligibility using registry data from the Diabetes Case Management Program (DCMP) at the CCH Diabetes Care Center between January 2007 and December 2017. The DCMP provides standardized comprehensive diabetes care including lifestyle assessment, physical examination, laboratory evaluation, and diabetes self-management (DSM) education (such as instruction on nutrition, diet, exercise, medication, self-monitoring of blood glucose (SMBG), and problem-solving skills aimed at reducing related complications). All participants in the program received education during scheduled teaching sessions. Care is delivered by a coordinated multidisciplinary team, including physicians, and certified diabetes educators (registered nurses and dietitians). A detailed description of the program has been reported elsewhere ( 24 ). The diagnosis of T2DM was based on the criteria established by the American Diabetes Association, by satisfying one of the following: a fasting plasma glucose value ≥ 126 mg/dL, a 2-h plasma glucose ≥ 200 mg/dL during a 75-g oral glucose tolerance test, a random plasma glucose ≥ 200 mg/dL in a patient with classic symptoms of hyperglycemia, or a glycated hemoglobin (HbA1c) level of ≥ 6.5%. Excluded from the study were individuals with type 1 and other types of diabetes (n = 49), those with less than 3 years of analyzable data (n = 3926), diabetes duration exceeding 12 months at enrollment (n = 15990), pregnancy (n = 1), baseline HbA1c < 7 (n = 1010), no anti-diabetic medication treatment (n = 270), DKA/HHS during 3 years (n = 35), age below 18 or above 70 (n = 1020), and an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m 2 (n = 72). The analysis encompassed 1256 eligible patients, with 1142 in the oral antidiabetic therapy group and 114 in the early insulinization group, following 1:1 propensity score matching to mitigate bias (Fig. 1 ). Methods were performed in accordance with the relevant guidelines and regulations. The Institutional Review Board of CCH granted the waiver for informed consent and approved the study (IRB No: 210318). Data collection. Data were collected from the hospital's electronic medical records, including the DCMP diabetes registry, prescriptions, laboratory data, and CCH research database. Patients with type 2 diabetes were referred to the Diabetes Care Center by diabetes specialists, typically 2 to 6 weeks after their first outpatient clinic visit. Upon enrollment in the DCMP, patients underwent comprehensive assessments, including surveys, physical examinations, and laboratory tests. They received standardized one-on-one diabetes self-management education sessions. A certified diabetes educator evaluated patients' knowledge on glycemic control, willingness towards DSM, frequency of SMBG, and medication adherence through face-to-face interviews post-course ( 24 ). Outcome variables. Glycemic control, the primary outcome, was assessed using HbA1c levels measured at baseline and at 3, 6, 9, 12, 24, and 36 months post-enrollment, measured through ion-exchange high-performance liquid chromatography using the VARIANTTM II Turbo system . Major exposure variables. Participants who received early insulinization for 3 to 6 months were in the insulin group, while those receiving OADs alone were in the OAD group. Variables for subgroup analysis. Participants were categorized based on HbA1c levels (< 9.0% or ≥ 9.0%), sex (male or female), BMI (< 30 kg/m 2 or ≥ 30 kg/m 2 ), and age at onset of diabetes (< 40 or ≥ 40). Other control variables . Basic data included age at onset of diabetes, gender, education level, and family history of diabetes. Health-related behaviors included smoking (within the preceding year), alcohol consumption (more than once weekly within the preceding year), and physical activity [regular (≥ 30 min/day, ≥ 3 days/week), occasional (less rigorous than regular exercise), or no exercise]. Knowledge regarding glycemic control was defined as an understanding of the need for and methods of controlling blood glucose. Willingness toward DSM was defined as the motivation to learn self-management techniques. Medication adherence was defined as taking medication regularly at the dose recommended by the physician over the past week. Four-point scales were used to assess the three aforementioned variables. Data were merged into simple dichotomies (i.e., top-two-box vs. bottom-two-box) and categorized as adequate (yes) or inadequate (no) for analysis ( 24 ). Physical examination included measurement of blood pressure (BP), height, and body weight. Systolic and diastolic BP were measured with the patients in a seated position after a 10-min rest. Body mass index was calculated as body weight (kg)/height (m 2 ). Baseline laboratory data included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), creatinine, and glutamic pyruvic transaminase (GPT) levels measured using a UniCel DxC 800 Synchron Clinical System (Beckman Coulter, Brea, CA, USA). eGFR was calculated using the equation recommended by the National Kidney Foundation. Data on the major non-psychiatric comorbidities described in the Charlson Comorbidity Index (CCI) during the year preceding enrolment were collected from the CCH research database. Major comorbidities, including congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accident (CVA), hypertension (HTN), hyperlipidemia, chronic kidney disease (CKD), cancer, cirrhosis, rheumatoid arthritis (RA), myocardial infarction (MI), peripheral vascular disease (PVD) and dysrhythmia were analyzed as independent variables ( 24 ). Statistical analysis. Frequency counts with percentages and mean ± standard deviation (SD) were used to describe categorical and continuous variables, respectively. Differences between the two groups were assessed using the chi-square test for categorical variables and the Student’s t-test for continuous variables. To mitigate the influence of confounding variables, we employed 1:1 propensity score matching. Kaplan-Meier method was utilized to generate cumulative incidence curves for well-controlled events, and discrepancies between these curves were assessed using log-rank tests. Cox proportional hazard models were employed to evaluate the relationship between insulin use status and well-controlled events. The multivariate Cox proportional regression model was adjusted for the propensity score. Hazard ratios (HR) with 95% confidence intervals (CI) were used to express the results. Subgroup analyses were conducted to evaluate the association between insulin and glycemic control in subgroups stratified by various HbA1c levels (≥ 9.0% or < 9.0%), sex (male or female), BMI (≥ 30 kg/m 2 or < 30 kg/m 2 ), and age at onset of diabetes (≥ 40 or < 40). All analyses were two-tailed and performed using IBM SPSS Statistics version 22 (IBM Corp., Armonk, NY, USA) and SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA). The significance level was set at 0.05. Results Characteristics of patients . Out of the 23,629 patients screened, 1,256 met the eligibility criteria. Following propensity score matching (1:1), each group consisted of 113 patients. The OAD group had an average age of 49.26 ± 10.67 years and an average BMI of 26.33 ± 4.07 kg/m 2 , while the insulin group had an average age of 48.77 ± 11.59 years and an average BMI of 26.22 ± 5.12 kg/m 2 (Table 1 ). Both groups shared similar demographic traits, encompassing age, sex, education level, family history of diabetes, smoking and alcohol consumption, physical activity, knowledge of glycemic control, willingness towards DSM, medication adherence, BMI, mean BP, total cholesterol, triglycerides, HDL, LDL, eGFR, GPT, comorbidities at baseline (such as CHF, CVA, CAD, HTN, hyperlipidemia, CKD, cancer, cirrhosis, RA, MI, PVD, and dysrhythmia) (Table 1 ). The baseline HbA1c levels were similar between the OAD and early insulinization groups (mean HbA1c 11.08 ± 2.29 vs.11.2 ± 2.21, p = 0.693) (Table 1 ). However, over the course of 36 months, the OAD consistently demonstrated lower HbA1c levels at 3, 12, 24, and 36 months compared to the early insulinization group. (HbA1c: 7.73 ± 1.93 vs. 8.1 ± 1.9, p = 0.138; 6.74 ± 1.37 vs. 7.46 ± 1.92, p = 0.001; 6.9 ± 1.11 vs. 7.46 ± 1.68, p = 0.003; 6.83 ± 1.12 vs. 7.44 ± 1.73, p = 0.002, respectively) (Table 2 ). After the index period, 78.8% in the OAD group and 67.3% of patients in the early insulinization group achieved glycemic control, with a marginally significant difference (p = 0.051) (Table 2 ). Time to control did not significantly differ between the OAD group (442.08 ± 350.06 days) and the early insulinization group (513.92 ± 388.93 days) (p = 0.146) (Table 2 ). The OAD group exhibited a higher incidence of well-controlled diabetes than the insulin group, but the difference was not statistically significant (p = 0.118, log-rank test) (Fig. 2 ). Table 1 Baseline demographic comparisons: analyzing characteristics, variables, and comorbidities in subjects with oral antidiabetic therapy versus early insulinization. Oral antidiabetic therapy Early insulinization P-value Sample size 113 113 Age (years) 49.26 ± 10.67 48.77 ± 11.59 0.743 Gender, Male 72(63.7%) 73(64.6%) 0.890 Level of education: No 3(2.7%) 5(4.4%) 0.884 Primary school 21(18.6%) 17(15%) Secondary or High school 56(49.6%) 58(51.3%) University or above 33(29.2%) 33(29.2%) Family history of DM: Yes 75(66.4%) 75(66.4%) 1 Current smoking 22(19.5%) 21(18.6%) 0.865 Alcohol drinking 1(0.9%) 3(2.7%) 0.313 Physical activity: No exercise 47(41.6%) 54(47.8%) 0.597 Occasional exercise 37(32.7%) 31(27.4%) Regular exercise 29(25.7%) 28(24.8%) Knowledge regarding GC: Yes 62(54.9%) 63(55.8%) 0.894 Willingness toward DSM: Yes 100(88.5%) 103(91.2%) 0.509 Perform SMBG: Yes 237(99.2%) 238(99.6%) 0.562 Medication adherence: Yes 109(96.5%) 110(97.3%) 0.701 Insulin secretagogues 68(60.2%) 38(33.6%) < 0.001 Non-insulin secretagogues 106(93.8%) 84(74.3%) < 0.001 Clinical variables HbA1c at baseline (%) 11.08 ± 2.29 11.2 ± 2.21 0.693 BMI (kg/m 2 ) 26.33 ± 4.07 26.22 ± 5.12 0.860 Mean BP (mmHg) 96.31 ± 10.4 96.08 ± 11.02 0.874 Total cholesterol (mg/dL) 178.27 ± 40.33 176.9 ± 41 0.801 Triglycerides (mg/dL) 126.88 ± 104.63 128.59 ± 80.97 0.891 HDL (mg/dL) 45.79 ± 11.35 46.1 ± 13.03 0.849 LDL (mg/dL) 109.04 ± 34.47 106.2 ± 35.8 0.544 eGFR (mL/min/1.73m 2 ) 101.67 ± 27.57 107.28 ± 40.43 0.224 GPT 39.19 ± 39.31 37.35 ± 40.69 0.730 Comorbidity at baseline CHF 9(8%) 9(8%) 1 CVA 3(2.7%) 3(2.7%) 1 CAD 3(2.7%) 4(3.5%) 0.701 HTN 50(44.2%) 52(46%) 0.789 Hyperlipidemia 60(53.1%) 64(56.6%) 0.593 CKD 1(0.9%) 2(1.8%) 0.561 Cancer 1(0.9%) 2(1.8%) 0.561 Cirrhosis 4(3.5%) 4(3.5%) 1 Rheumatoid arthritis 2(1.8%) 2(1.8%) 1 Myocardial infarction 0(0%) 1(0.9%) 0.316 PVD 0(0%) 1(0.9%) 0.316 Dysrhythmia 0(0%) 0(0%) - Note. Results are expressed as mean ± SD or n (%). Abbreviations: DM, diabetes mellitus; GC, glycemic control; DSM, diabetes self-management; SMBG, self-monitoring of blood glucose; HbA1c, hemoglobin A1c; BMI, body mass index; BP, blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; GPT, glutamic pyruvic transaminase; CHF, congestive heart failure; CAD, coronary artery disease; CVA, cerebrovascular accident; CKD, chronic kidney disease; PVD, peripheral vascular disease. Table 2 Oral antidiabetic therapy versus early insulinization on glycemic control after propensity score matching. Oral antidiabetic therapy Early insulinization P-value Sample size 113 113 Clinical variables HbA1c at baseline (%) 11.08 ± 2.29 11.2 ± 2.21 0.693 HbA1c at 3-month (%) 7.73 ± 1.93 8.1 ± 1.9 0.138 HbA1c at 6-month (%) 6.72 ± 1.32 7.35 ± 1.96 0.005 HbA1c at 9-month (%) 6.68 ± 1.5 7.48 ± 1.99 0.001 HbA1c at 12-month (%) 6.74 ± 1.37 7.46 ± 1.92 0.001 HbA1c at 18-month (%) 6.86 ± 1.24 7.47 ± 1.7 0.002 HbA1c at 24-month (%) 6.9 ± 1.11 7.46 ± 1.68 0.003 HbA1c at 30-month (%) 6.97 ± 1.13 7.5 ± 1.44 0.003 HbA1c at 36-month (%) 6.83 ± 1.12 7.44 ± 1.73 0.002 Outcome after index date Well-controlled rate 89(78.8%) 76(67.3%) 0.051 Follow-up time Time to well-controlled (day) 442.08 ± 350.06 513.92 ± 388.93 0.146 Note. Results are expressed as mean ± SD or n (%). Abbreviations: HbA1c, hemoglobin A1c. Subgroup analyses revealed consistently higher rates of well-controlled diabetes in the OAD group compared to the early insulinization group across baseline HbA1c levels (< 9.0%: aHR: 2.10, p = 0.055; ≥9.0%: aHR: 1.12, p = 0.496), gender (males: aHR: 1.16, p = 0.425; females: aHR: 1.53, p = 0.128), and BMI (< 30 kg/m 2 : aHR: 1.29, p = 0.133; ≥30 kg/m 2 : aHR: 1.51, p = 0.339) (Table 3 ). However, these differences did not reach statistical significance. In participants with diabetes onset before age 40, the OAD group showed slightly lower incidence of well-controlled diabetes (aHR = 0.93, p = 0.817). (Table 3 ). Table 3 Subgroup analysis of well-controlled type 2 diabetes in oral antidiabetic therapy versus early insulinization. Subgroup n cHR (95% CI) P-value aHR* (95% CI) P-value HbA1c < 9% 44 2.11 (0.99,4.49) 0.054 2.10 (0.99,4.48) 0.055 \(\ge\) 9% 182 1.11 (0.80,1.56) 0.530 1.12 (0.80,1.57) 0.496 Gender Male 145 1.15 (0.79,1.67) 0.460 1.16 (0.80,1.69) 0.425 Female 81 1.53 (0.89,2.63) 0.127 1.53 (0.89,2.63) 0.128 Age < 40 55 0.93 (0.51,1.71) 0.814 0.93 (0.50,1.72) 0.817 \(\ge\) 40 171 1.42 (0.99,2.02) 0.057 1.40 (0.98,2.00) 0.066 BMI \(<\) 30 186 1.30 (0.93,1.81) 0.124 1.29 (0.93,1.80) 0.133 \(\ge\) 30 40 1.19 (0.54,2.61) 0.666 1.51 (0.65,3.50) 0.339 Note. *Adjusted for propensity score. In general, irrespective of glycemic control (HbA1c < 9.0% or ≥ 9.0%), gender (male or female), diabetes onset age (age < 40 or ≥ 40), and BMI (BMI < 30 kg/m 2 or ≥ 30 kg/m 2 ), the OAD group exhibited a more substantial reduction in HbA1c levels compared to the insulin group (Fig. 3 ). Discussion We found that oral antidiabetic therapy was not inferior to early insulinization on glycemic control in newly diagnosed type 2 diabetes patients, irrespective of baseline HbA1c, BMI, sex and age. While the initial baseline HbA1c levels of our study participants were notably elevated (ranging from 11.08 to 11.2%), the group receiving oral antidiabetic therapy demonstrated more significant reductions in HbA1c levels over the course of 3, 12, 24, and 36 months. This led to a higher rates of well-controlled glycemic levels (78.8% vs. 67.3%), and a shorter timeframe (442.08 ± 350.06 vs. 513.92 ± 388.93 days) in OAD group compared to early insulinization group. Our study findings differ from prior investigations conducted by Weng et al., Ryan et al., and Karacaer et al. ( 8 , 9 , 25 ), which showed a greater percentage of patients attaining target glycemic control within a shorter timeframe in the insulin group compared to those receiving OADs. Their methods involved continuous subcutaneous infusion insulin (CS II) or multiple daily insulin injections (MDI) with daily dosage adjustments ( 8 , 9 , 25 ), contrasting our insulin approach characterized by reduced intensity of injection and monitoring. In newly diagnosed type 2 diabetes patients, early insulinization is beneficial with high-intensity titration and monitoring, otherwise, oral antidiabetic therapy may be a suitable alternative. In the past two decades, oral antidiabetic drugs (OADs) have undergone significant advancements. DeFronzo's 'ominous octet' delineates eight factors contributing to the pathophysiology of type 2 diabetes, advocating combination therapy involving diet, exercise, metformin, thiazolidinediones (TZD), and glucagon-like peptide-1 (GLP-1) receptor agonists. This approach aims to enhance insulin sensitivity, preserve β-cell function, and facilitate weight loss in individuals with type 2 diabetes ( 23 ). Inadequate dose adjustment and monitoring of insulin therapy may increase the risk of hypoglycemia and weight gain compared to OADs alone, potentially undermining insulin's benefits. Although both groups in our study demonstrated similar rates of SMBG (99.2% vs. 99.6%), this measure alone may not fully capture the intensity and frequency of SMBG practices. Variations in self-monitoring of blood glucose (SMBG) patterns have a notable impact on physicians' decisions regarding medication regimens, particularly within the insulin-treated group ( 26 ). Such variations have the potential to worsen clinician inertia. For individuals newly diagnosed with type 2 diabetes, it is essential to prioritize addressing the underlying pathophysiological defect by implementing suitable medications, lifestyle adjustments, and self-management strategies. This comprehensive approach should be prioritized over relying solely on early insulinization. Subgroup analysis revealed a significantly higher rate of well-controlled cases among those with a baseline HbA1c < 9.0% using OADs alone (HR: 2.10, p = 0.055) compared to those undergoing early insulinization. Although not achieving statistical significance, this implies that OADs alone might be more favorable for individuals with lower baseline HbA1c levels. This observation aligns with current guidelines ( 27 ). Our study's strength lies in its utilization of longitudinal data, which establishes a temporal relationship between medical therapy and glycemic control. This approach mitigates the potential for reverse causality, a limitation often encountered in cross-sectional studies. This study has notable limitations that warrant acknowledgment. First, the extensive time span of patient enrollment from 2007 to 2017 has resulted in diverse insulin regimens and variations in oral antidiabetic agents, which may ultimately underestimate our study outcomes. Second, the study's capacity to establish a clear causal relationship is restricted due to the absence of randomization. However, the utilization of propensity score matching has mitigated the potential for selection bias and addressed the effects of confounders. Third, as a retrospective study, the causal interpretation of this study was limited. Last, the potential impact of certain unmeasured confounding factors on the observed association cannot be definitively excluded. For instance, the precise effects of dietary habits, actual intensity of physical activity, intensity of self-monitoring of blood glucose (SMBG), frequency and severity of hypoglycemia, and changes in body weight on our study population remain unclear. Conclusions Early insulinization may not significantly enhance glycemic control in newly diagnosed type 2 diabetes patients compared to utilizing OADs alone. Simply initiating insulin early is insufficient; attaining optimal control necessitates a structured insulin titration protocol and diligent self-monitoring of blood glucose. Our real-world data support considering oral antidiabetic therapy as a reasonable treatment option for newly diagnosed type 2 diabetes patients, even those with elevated baseline HbA1c levels. Declarations Acknowledgements: We appreciate the method descriptions provided by Hon‑Ke Sia, Chew‑Teng Kor, Shih‑TeTu et al. Authors' contributions: The study was conceived and designed by YM Lee, data analysis was performed by LP Ru, and manuscript composition was contributed to by HK Sia. Final manuscript approval was given by Sia and Lee. Informed consent statement: Though written informed consent was not provided by the participants for the use of their medical records in this study, the patient records have been de-identified and anonymized prior to investigation. The work was approved our institutional review board or equivalent body (IRB No: 210318). Consent for publication: All authors read and approved the final manuscript. Competing interests: The authors declare that they have no competing interests. Data availability: The dataset utilized in the study is not accessible due to confidentiality regulations outlined in the Personal Information Protection Act enforced by the Taiwanese Government since 2012. For additional details regarding data acquisition, interested parties may contact the primary author upon request. References Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. Deshpande AD, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther. 2008;88(11):1254-64. 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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-3999987","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":280477928,"identity":"f7c77c74-fe26-4aeb-82f3-b90192efea32","order_by":0,"name":"Yang-Ming Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYBACNvb+579/VNgwMEgQq4WP5wyDNMOZNLgWwjrlJHIYpBlbDpOghY0h94BxYcN5ef7ZDYyPK34x1BkcIKjlXELyzB23DWfcOcBseLaPQYKwFsYGgwO8Z24nGEgksEk29jBImBHUwsxg2MDbdo4ULWw8xsy8bQcgWhp+EKOFhy2NccaZZMMZNxKbDRsbJCT3E9IiP//xMYYPFXby/DOSDz5s+GPDL9lAQAsSYGxgYGwjOg3AwR+SdYyCUTAKRsEIAAD3Dj3maVx5YgAAAABJRU5ErkJggg==","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yang-Ming","middleName":"","lastName":"Lee","suffix":""},{"id":280477929,"identity":"3a325bed-5831-4c77-8b6d-7a04e656c10e","order_by":1,"name":"Lin Ru","email":"","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Ru","suffix":""},{"id":280477930,"identity":"525e90e0-6020-490f-b247-eff863a14ee1","order_by":2,"name":"Hon-Ke Sia","email":"","orcid":"","institution":"Changhua Christian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hon-Ke","middleName":"","lastName":"Sia","suffix":""}],"badges":[],"createdAt":"2024-02-29 13:59:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3999987/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3999987/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53007014,"identity":"7fa6bd78-f49e-4d5b-8ab7-a619c68b8934","added_by":"auto","created_at":"2024-03-19 15:12:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":676740,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study population. CCH, Changhua Christian Hospital; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin; DKA, diabetic ketoacidosis; HHS, hyperglycemic hyperosmolar state.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3999987/v1/8f72dfe777bd78098b812e96.png"},{"id":53007013,"identity":"403e8896-361b-4ca2-8154-5b23d217140b","added_by":"auto","created_at":"2024-03-19 15:12:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":29037,"visible":true,"origin":"","legend":"\u003cp\u003eIllustrating that the cumulative incidence of well-controlled diabetes between the OAD and early insulinization groups.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3999987/v1/fbab2660f89f4bb91f95b6d7.png"},{"id":53007011,"identity":"fd0d6b2c-a02f-4fc2-abed-85ddfeb8e237","added_by":"auto","created_at":"2024-03-19 15:12:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":32466,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of mean HbA1C levels at different visit between the OAD and early insulinization groups.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3999987/v1/8056ab5f97cb31f2e2809790.png"},{"id":53008969,"identity":"ff0712c2-73d7-46da-8a44-f2d15ab5be28","added_by":"auto","created_at":"2024-03-19 15:20:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":609890,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3999987/v1/ceef3cca-ce0f-471f-97e1-3d9635ef3a04.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Oral antidiabetic therapy versus early insulinization on glycemic control in newly diagnosed type 2 diabetes patients: a retrospective matched cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDiabetes stands as a growing global pandemic characterized by escalating prevalence rates and enduring chronic complications associated with hyperglycemia. Complications include retinopathy, neuropathy, nephropathy, and cardiovascular disease, imposing significant socioeconomic burdens (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The United Kingdom Prospective Diabetes Study (UKPDS) and the Diabetes Control and Complications Trial (DCCT) highlighted \"metabolic memory,\" revealing that early glycemic control in diabetes offers lasting end-organ protection, independent of subsequent treatment or control quality (\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). This emphasizes the vital need for timely and optimal glycemic control to prevent diabetes-related complications.\u003c/p\u003e \u003cp\u003eIntensive short-term insulin therapy has been shown to induce glycemic remission in severe, newly diagnosed type 2 diabetes patients (\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Despite the availability of oral antidiabetic drugs (OADs), insulin remains the most potent treatment, providing established benefits including mitigating glucotoxicity, suppressing lipotoxicity, dampening inflammation, abolishing reactive oxygen species (ROS), fostering β-cell recovery, preserving functionality, and bolstering insulin sensitivity (\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). However, challenges and barriers associated with insulin therapy, including the risk of hypoglycemia, weight gain, injection anxieties, and logistical inconveniences, may discourage its initiation. Type 2 diabetes is a complex metabolic disorder marked by heightened insulin resistance and diminished β-cell function, exhibiting multifaceted and diverse characteristics (\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). It is influenced by a multitude of risk factors, including sedentary lifestyle, dietary habits, obesity, aging, familial predisposition, and ethnic background (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). DeFronzo proposed prioritizing the reversal of established pathogenic abnormalities in type 2 diabetes by combining multiple drugs (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Since 2000, various OADs targeting diverse mechanisms have been developed. Thus, for newly diagnosed type 2 diabetes patients, OADs alone may be comparable to early insulinization, before the onset of β-cell failure. Our real-world study aims to compare oral antidiabetic therapy versus early insulinization for glycemic control in these patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e \u003cb\u003eSubjects\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThis retrospective cohort study was conducted at the Changhua Christian Hospital (CCH), Taiwan. A total of 23629 patients with type 2 diabetes were screened for eligibility using registry data from the Diabetes Case Management Program (DCMP) at the CCH Diabetes Care Center between January 2007 and December 2017. The DCMP provides standardized comprehensive diabetes care including lifestyle assessment, physical examination, laboratory evaluation, and diabetes self-management (DSM) education (such as instruction on nutrition, diet, exercise, medication, self-monitoring of blood glucose (SMBG), and problem-solving skills aimed at reducing related complications). All participants in the program received education during scheduled teaching sessions. Care is delivered by a coordinated multidisciplinary team, including physicians, and certified diabetes educators (registered nurses and dietitians). A detailed description of the program has been reported elsewhere (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). The diagnosis of T2DM was based on the criteria established by the American Diabetes Association, by satisfying one of the following: a fasting plasma glucose value\u0026thinsp;\u0026ge;\u0026thinsp;126 mg/dL, a 2-h plasma glucose\u0026thinsp;\u0026ge;\u0026thinsp;200 mg/dL during a 75-g oral glucose tolerance test, a random plasma glucose\u0026thinsp;\u0026ge;\u0026thinsp;200 mg/dL in a patient with classic symptoms of hyperglycemia, or a glycated hemoglobin (HbA1c) level of \u0026ge;\u0026thinsp;6.5%. Excluded from the study were individuals with type 1 and other types of diabetes (n\u0026thinsp;=\u0026thinsp;49), those with less than 3 years of analyzable data (n\u0026thinsp;=\u0026thinsp;3926), diabetes duration exceeding 12 months at enrollment (n\u0026thinsp;=\u0026thinsp;15990), pregnancy (n\u0026thinsp;=\u0026thinsp;1), baseline HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;7 (n\u0026thinsp;=\u0026thinsp;1010), no anti-diabetic medication treatment (n\u0026thinsp;=\u0026thinsp;270), DKA/HHS during 3 years (n\u0026thinsp;=\u0026thinsp;35), age below 18 or above 70 (n\u0026thinsp;=\u0026thinsp;1020), and an estimated glomerular filtration rate (eGFR)\u0026thinsp;\u0026lt;\u0026thinsp;30 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e (n\u0026thinsp;=\u0026thinsp;72). The analysis encompassed 1256 eligible patients, with 1142 in the oral antidiabetic therapy group and 114 in the early insulinization group, following 1:1 propensity score matching to mitigate bias (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Methods were performed in accordance with the relevant guidelines and regulations. The Institutional Review Board of CCH granted the waiver for informed consent and approved the study (IRB No: 210318).\u003c/p\u003e \u003cp\u003e \u003cb\u003eData collection.\u003c/b\u003e Data were collected from the hospital's electronic medical records, including the DCMP diabetes registry, prescriptions, laboratory data, and CCH research database. Patients with type 2 diabetes were referred to the Diabetes Care Center by diabetes specialists, typically 2 to 6 weeks after their first outpatient clinic visit. Upon enrollment in the DCMP, patients underwent comprehensive assessments, including surveys, physical examinations, and laboratory tests. They received standardized one-on-one diabetes self-management education sessions. A certified diabetes educator evaluated patients' knowledge on glycemic control, willingness towards DSM, frequency of SMBG, and medication adherence through face-to-face interviews post-course (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eOutcome variables.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eGlycemic control, the primary outcome, was assessed using HbA1c levels measured at baseline and at 3, 6, 9, 12, 24, and 36 months post-enrollment, measured through ion-exchange high-performance liquid chromatography using the VARIANTTM II Turbo system .\u003c/p\u003e \u003cp\u003e \u003cb\u003eMajor exposure variables.\u003c/b\u003e Participants who received early insulinization for 3 to 6 months were in the insulin group, while those receiving OADs alone were in the OAD group.\u003c/p\u003e \u003cp\u003e \u003cb\u003eVariables for subgroup analysis.\u003c/b\u003e Participants were categorized based on HbA1c levels (\u0026lt;\u0026thinsp;9.0% or \u0026ge;\u0026thinsp;9.0%), sex (male or female), BMI (\u0026lt;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e or \u0026ge;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e), and age at onset of diabetes (\u0026lt;\u0026thinsp;40 or \u0026ge;\u0026thinsp;40).\u003c/p\u003e \u003cp\u003e \u003cb\u003eOther control variables\u003c/b\u003e. Basic data included age at onset of diabetes, gender, education level, and family history of diabetes. Health-related behaviors included smoking (within the preceding year), alcohol consumption (more than once weekly within the preceding year), and physical activity [regular (\u0026ge;\u0026thinsp;30 min/day, \u0026ge; 3 days/week), occasional (less rigorous than regular exercise), or no exercise]. Knowledge regarding glycemic control was defined as an understanding of the need for and methods of controlling blood glucose. Willingness toward DSM was defined as the motivation to learn self-management techniques. Medication adherence was defined as taking medication regularly at the dose recommended by the physician over the past week. Four-point scales were used to assess the three aforementioned variables. Data were merged into simple dichotomies (i.e., top-two-box vs. bottom-two-box) and categorized as adequate (yes) or inadequate (no) for analysis (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePhysical examination included measurement of blood pressure (BP), height, and body weight. Systolic and diastolic BP were measured with the patients in a seated position after a 10-min rest. Body mass index was calculated as body weight (kg)/height (m\u003csup\u003e2\u003c/sup\u003e). Baseline laboratory data included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), creatinine, and glutamic pyruvic transaminase (GPT) levels measured using a UniCel DxC 800 Synchron Clinical System (Beckman Coulter, Brea, CA, USA). eGFR was calculated using the equation recommended by the National Kidney Foundation. Data on the major non-psychiatric comorbidities described in the Charlson Comorbidity Index (CCI) during the year preceding enrolment were collected from the CCH research database. Major comorbidities, including congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accident (CVA), hypertension (HTN), hyperlipidemia, chronic kidney disease (CKD), cancer, cirrhosis, rheumatoid arthritis (RA), myocardial infarction (MI), peripheral vascular disease (PVD) and dysrhythmia were analyzed as independent variables (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analysis.\u003c/b\u003e Frequency counts with percentages and mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) were used to describe categorical and continuous variables, respectively. Differences between the two groups were assessed using the chi-square test for categorical variables and the Student\u0026rsquo;s t-test for continuous variables. To mitigate the influence of confounding variables, we employed 1:1 propensity score matching. Kaplan-Meier method was utilized to generate cumulative incidence curves for well-controlled events, and discrepancies between these curves were assessed using log-rank tests. Cox proportional hazard models were employed to evaluate the relationship between insulin use status and well-controlled events. The multivariate Cox proportional regression model was adjusted for the propensity score. Hazard ratios (HR) with 95% confidence intervals (CI) were used to express the results. Subgroup analyses were conducted to evaluate the association between insulin and glycemic control in subgroups stratified by various HbA1c levels (\u0026ge;\u0026thinsp;9.0% or \u0026lt;\u0026thinsp;9.0%), sex (male or female), BMI (\u0026ge;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e or \u0026lt;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e), and age at onset of diabetes (\u0026ge;\u0026thinsp;40 or \u0026lt;\u0026thinsp;40). All analyses were two-tailed and performed using IBM SPSS Statistics version 22 (IBM Corp., Armonk, NY, USA) and SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA). The significance level was set at 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eCharacteristics of patients\u003c/strong\u003e. Out of the 23,629 patients screened, 1,256 met the eligibility criteria. Following propensity score matching (1:1), each group consisted of 113 patients. The OAD group had an average age of 49.26\u0026thinsp;\u0026plusmn;\u0026thinsp;10.67 years and an average BMI of 26.33\u0026thinsp;\u0026plusmn;\u0026thinsp;4.07 kg/m\u003csup\u003e2\u003c/sup\u003e, while the insulin group had an average age of 48.77\u0026thinsp;\u0026plusmn;\u0026thinsp;11.59 years and an average BMI of 26.22\u0026thinsp;\u0026plusmn;\u0026thinsp;5.12 kg/m\u003csup\u003e2\u003c/sup\u003e (Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e). Both groups shared similar demographic traits, encompassing age, sex, education level, family history of diabetes, smoking and alcohol consumption, physical activity, knowledge of glycemic control, willingness towards DSM, medication adherence, BMI, mean BP, total cholesterol, triglycerides, HDL, LDL, eGFR, GPT, comorbidities at baseline (such as CHF, CVA, CAD, HTN, hyperlipidemia, CKD, cancer, cirrhosis, RA, MI, PVD, and dysrhythmia) (Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e). The baseline HbA1c levels were similar between the OAD and early insulinization groups (mean HbA1c 11.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.29 vs.11.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21, p\u0026thinsp;=\u0026thinsp;0.693) (Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e). However, over the course of 36 months, the OAD consistently demonstrated lower HbA1c levels at 3, 12, 24, and 36 months compared to the early insulinization group. (HbA1c: 7.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.93 vs. 8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9, p\u0026thinsp;=\u0026thinsp;0.138; 6.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37 vs. 7.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92, p\u0026thinsp;=\u0026thinsp;0.001; 6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11 vs. 7.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68, p\u0026thinsp;=\u0026thinsp;0.003; 6.83\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12 vs. 7.44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73, p\u0026thinsp;=\u0026thinsp;0.002, respectively) (Table\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e). After the index period, 78.8% in the OAD group and 67.3% of patients in the early insulinization group achieved glycemic control, with a marginally significant difference (p\u0026thinsp;=\u0026thinsp;0.051) (Table\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e). Time to control did not significantly differ between the OAD group (442.08\u0026thinsp;\u0026plusmn;\u0026thinsp;350.06 days) and the early insulinization group (513.92\u0026thinsp;\u0026plusmn;\u0026thinsp;388.93 days) (p\u0026thinsp;=\u0026thinsp;0.146) (Table\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e). The OAD group exhibited a higher incidence of well-controlled diabetes than the insulin group, but the difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.118, log-rank test) (Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBaseline demographic comparisons: analyzing characteristics, variables, and comorbidities in subjects with oral antidiabetic therapy versus early insulinization.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOral antidiabetic therapy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEarly insulinization\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.26\u0026thinsp;\u0026plusmn;\u0026thinsp;10.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.77\u0026thinsp;\u0026plusmn;\u0026thinsp;11.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.743\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender, Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72(63.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73(64.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.890\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLevel of education: No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.884\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(18.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecondary or High school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56(49.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58(51.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUniversity or above\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(29.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(29.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFamily history of DM: Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75(66.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75(66.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCurrent smoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(19.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(18.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.865\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlcohol drinking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhysical activity: No exercise\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47(41.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54(47.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.597\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOccasional exercise\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37(32.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31(27.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRegular exercise\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29(25.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(24.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKnowledge regarding GC: Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62(54.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63(55.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.894\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWillingness toward DSM: Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100(88.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e103(91.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.509\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePerform SMBG: Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e237(99.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e238(99.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.562\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedication adherence: Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e109(96.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e110(97.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.701\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInsulin secretagogues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68(60.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38(33.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-insulin secretagogues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e106(93.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84(74.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical variables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at baseline (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.693\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.33\u0026thinsp;\u0026plusmn;\u0026thinsp;4.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.22\u0026thinsp;\u0026plusmn;\u0026thinsp;5.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.860\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean BP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.31\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.08\u0026thinsp;\u0026plusmn;\u0026thinsp;11.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.874\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal cholesterol (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e178.27\u0026thinsp;\u0026plusmn;\u0026thinsp;40.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e176.9\u0026thinsp;\u0026plusmn;\u0026thinsp;41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.801\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTriglycerides (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e126.88\u0026thinsp;\u0026plusmn;\u0026thinsp;104.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e128.59\u0026thinsp;\u0026plusmn;\u0026thinsp;80.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHDL (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.79\u0026thinsp;\u0026plusmn;\u0026thinsp;11.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLDL (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e109.04\u0026thinsp;\u0026plusmn;\u0026thinsp;34.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e106.2\u0026thinsp;\u0026plusmn;\u0026thinsp;35.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.544\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eeGFR (mL/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101.67\u0026thinsp;\u0026plusmn;\u0026thinsp;27.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e107.28\u0026thinsp;\u0026plusmn;\u0026thinsp;40.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.224\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.19\u0026thinsp;\u0026plusmn;\u0026thinsp;39.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.35\u0026thinsp;\u0026plusmn;\u0026thinsp;40.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.730\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidity at baseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.701\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50(44.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52(46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.789\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHyperlipidemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60(53.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64(56.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.593\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCKD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.561\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.561\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRheumatoid arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMyocardial infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.316\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.316\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDysrhythmia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eNote. Results are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or n (%). Abbreviations: DM, diabetes mellitus; GC, glycemic control; DSM, diabetes self-management; SMBG, self-monitoring of blood glucose; HbA1c, hemoglobin A1c; BMI, body mass index; BP, blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; GPT, glutamic pyruvic transaminase; CHF, congestive heart failure; CAD, coronary artery disease; CVA, cerebrovascular accident; CKD, chronic kidney disease; PVD, peripheral vascular disease.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv\u003e\n\u003c/div\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eOral antidiabetic therapy versus early insulinization on glycemic control after propensity score matching.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOral antidiabetic therapy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEarly insulinization\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical variables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at baseline (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.693\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at 3-month (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at 6-month (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at 9-month (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.68\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.48\u0026thinsp;\u0026plusmn;\u0026thinsp;1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at 12-month (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at 18-month (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.86\u0026thinsp;\u0026plusmn;\u0026thinsp;1.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.47\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at 24-month (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at 30-month (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c at 36-month (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.83\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome after index date\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWell-controlled rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89(78.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76(67.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFollow-up time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime to well-controlled (day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e442.08\u0026thinsp;\u0026plusmn;\u0026thinsp;350.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e513.92\u0026thinsp;\u0026plusmn;\u0026thinsp;388.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.146\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eNote. Results are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or n (%). Abbreviations: HbA1c, hemoglobin A1c.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eSubgroup analyses revealed consistently higher rates of well-controlled diabetes in the OAD group compared to the early insulinization group across baseline HbA1c levels (\u0026lt;\u0026thinsp;9.0%: aHR: 2.10, p\u0026thinsp;=\u0026thinsp;0.055; \u0026ge;9.0%: aHR: 1.12, p\u0026thinsp;=\u0026thinsp;0.496), gender (males: aHR: 1.16, p\u0026thinsp;=\u0026thinsp;0.425; females: aHR: 1.53, p\u0026thinsp;=\u0026thinsp;0.128), and BMI (\u0026lt;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e: aHR: 1.29, p\u0026thinsp;=\u0026thinsp;0.133; \u0026ge;30 kg/m\u003csup\u003e2\u003c/sup\u003e: aHR: 1.51, p\u0026thinsp;=\u0026thinsp;0.339) (Table\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e). However, these differences did not reach statistical significance. In participants with diabetes onset before age 40, the OAD group showed slightly lower incidence of well-controlled diabetes (aHR\u0026thinsp;=\u0026thinsp;0.93, p\u0026thinsp;=\u0026thinsp;0.817). (Table\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eSubgroup analysis of well-controlled type 2 diabetes in oral antidiabetic therapy versus early insulinization.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSubgroup\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ecHR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eaHR* (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.11 (0.99,4.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.10 (0.99,4.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cspan\u003e\u003cspan\u003e\\(\\ge\\)\u003c/span\u003e\u003c/span\u003e9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.11 (0.80,1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.530\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.12 (0.80,1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.496\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.15 (0.79,1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.460\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.16 (0.80,1.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.425\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.53 (0.89,2.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.53 (0.89,2.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.128\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.93 (0.51,1.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.814\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.93 (0.50,1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.817\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cspan\u003e\u003cspan\u003e\\(\\ge\\)\u003c/span\u003e\u003c/span\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.42 (0.99,2.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.40 (0.98,2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cspan\u003e\u003cspan\u003e\\(\u0026lt;\\)\u003c/span\u003e\u003c/span\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.30 (0.93,1.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.29 (0.93,1.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cspan\u003e\u003cspan\u003e\\(\\ge\\)\u003c/span\u003e\u003c/span\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.19 (0.54,2.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.666\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.51 (0.65,3.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.339\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eNote. *Adjusted for propensity score.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eIn general, irrespective of glycemic control (HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;9.0% or \u0026ge;\u0026thinsp;9.0%), gender (male or female), diabetes onset age (age\u0026thinsp;\u0026lt;\u0026thinsp;40 or \u0026ge;\u0026thinsp;40), and BMI (BMI\u0026thinsp;\u0026lt;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e or \u0026ge;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e), the OAD group exhibited a more substantial reduction in HbA1c levels compared to the insulin group (Fig.\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe found that oral antidiabetic therapy was not inferior to early insulinization on glycemic control in newly diagnosed type 2 diabetes patients, irrespective of baseline HbA1c, BMI, sex and age. While the initial baseline HbA1c levels of our study participants were notably elevated (ranging from 11.08 to 11.2%), the group receiving oral antidiabetic therapy demonstrated more significant reductions in HbA1c levels over the course of 3, 12, 24, and 36 months. This led to a higher rates of well-controlled glycemic levels (78.8% vs. 67.3%), and a shorter timeframe (442.08\u0026thinsp;\u0026plusmn;\u0026thinsp;350.06 vs. 513.92\u0026thinsp;\u0026plusmn;\u0026thinsp;388.93 days) in OAD group compared to early insulinization group.\u003c/p\u003e \u003cp\u003eOur study findings differ from prior investigations conducted by Weng et al., Ryan et al., and Karacaer et al. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), which showed a greater percentage of patients attaining target glycemic control within a shorter timeframe in the insulin group compared to those receiving OADs. Their methods involved continuous subcutaneous infusion insulin (CS II) or multiple daily insulin injections (MDI) with daily dosage adjustments (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), contrasting our insulin approach characterized by reduced intensity of injection and monitoring. In newly diagnosed type 2 diabetes patients, early insulinization is beneficial with high-intensity titration and monitoring, otherwise, oral antidiabetic therapy may be a suitable alternative.\u003c/p\u003e \u003cp\u003eIn the past two decades, oral antidiabetic drugs (OADs) have undergone significant advancements. DeFronzo's 'ominous octet' delineates eight factors contributing to the pathophysiology of type 2 diabetes, advocating combination therapy involving diet, exercise, metformin, thiazolidinediones (TZD), and glucagon-like peptide-1 (GLP-1) receptor agonists. This approach aims to enhance insulin sensitivity, preserve β-cell function, and facilitate weight loss in individuals with type 2 diabetes (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Inadequate dose adjustment and monitoring of insulin therapy may increase the risk of hypoglycemia and weight gain compared to OADs alone, potentially undermining insulin's benefits. Although both groups in our study demonstrated similar rates of SMBG (99.2% vs. 99.6%), this measure alone may not fully capture the intensity and frequency of SMBG practices. Variations in self-monitoring of blood glucose (SMBG) patterns have a notable impact on physicians' decisions regarding medication regimens, particularly within the insulin-treated group (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Such variations have the potential to worsen clinician inertia. For individuals newly diagnosed with type 2 diabetes, it is essential to prioritize addressing the underlying pathophysiological defect by implementing suitable medications, lifestyle adjustments, and self-management strategies. This comprehensive approach should be prioritized over relying solely on early insulinization.\u003c/p\u003e \u003cp\u003eSubgroup analysis revealed a significantly higher rate of well-controlled cases among those with a baseline HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;9.0% using OADs alone (HR: 2.10, p\u0026thinsp;=\u0026thinsp;0.055) compared to those undergoing early insulinization. Although not achieving statistical significance, this implies that OADs alone might be more favorable for individuals with lower baseline HbA1c levels. This observation aligns with current guidelines (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur study's strength lies in its utilization of longitudinal data, which establishes a temporal relationship between medical therapy and glycemic control. This approach mitigates the potential for reverse causality, a limitation often encountered in cross-sectional studies. This study has notable limitations that warrant acknowledgment. First, the extensive time span of patient enrollment from 2007 to 2017 has resulted in diverse insulin regimens and variations in oral antidiabetic agents, which may ultimately underestimate our study outcomes. Second, the study's capacity to establish a clear causal relationship is restricted due to the absence of randomization. However, the utilization of propensity score matching has mitigated the potential for selection bias and addressed the effects of confounders. Third, as a retrospective study, the causal interpretation of this study was limited.\u003c/p\u003e \u003cp\u003eLast, the potential impact of certain unmeasured confounding factors on the observed association cannot be definitively excluded. For instance, the precise effects of dietary habits, actual intensity of physical activity, intensity of self-monitoring of blood glucose (SMBG), frequency and severity of hypoglycemia, and changes in body weight on our study population remain unclear.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eEarly insulinization may not significantly enhance glycemic control in newly diagnosed type 2 diabetes patients compared to utilizing OADs alone. Simply initiating insulin early is insufficient; attaining optimal control necessitates a structured insulin titration protocol and diligent self-monitoring of blood glucose. Our real-world data support considering oral antidiabetic therapy as a reasonable treatment option for newly diagnosed type 2 diabetes patients, even those with elevated baseline HbA1c levels.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the method descriptions provided by Hon‑Ke Sia, Chew‑Teng Kor, Shih‑TeTu et al.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e The study was conceived and designed by YM Lee, data analysis was performed by LP Ru, and manuscript composition was contributed to by HK Sia. Final manuscript approval was given by Sia and Lee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent statement:\u003c/strong\u003e Though written informed consent was not provided by the participants for the use of their medical records in this study, the patient records have been de-identified and anonymized prior to investigation. The work was approved our institutional review board or equivalent body (IRB No: 210318).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e The dataset utilized in the study is not accessible due to confidentiality regulations outlined in the Personal Information Protection Act enforced by the Taiwanese Government since 2012. For additional details regarding data acquisition, interested parties may contact the primary author upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119.\u003c/li\u003e\n\u003cli\u003eDeshpande AD, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther. 2008;88(11):1254-64.\u003c/li\u003e\n\u003cli\u003eHarding JL, Pavkov ME, Magliano DJ, Shaw JE, Gregg EW. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019;62(1):3-16.\u003c/li\u003e\n\u003cli\u003eHolman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-89.\u003c/li\u003e\n\u003cli\u003ede Boer IH, Rue TC, Cleary PA, Lachin JM, Molitch ME, Steffes MW, et al. Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria: an analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. Arch Intern Med. 2011;171(5):412-20.\u003c/li\u003e\n\u003cli\u003eChalmers J, Cooper ME. UKPDS and the legacy effect. N Engl J Med. 2008;359(15):1618-20.\u003c/li\u003e\n\u003cli\u003eCeriello A. Hypothesis: the \u0026quot;metabolic memory\u0026quot;, the new challenge of diabetes. Diabetes Res Clin Pract. 2009;86 Suppl 1:S2-6.\u003c/li\u003e\n\u003cli\u003eWeng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet (London, England). 2008;371(9626):1753-60.\u003c/li\u003e\n\u003cli\u003eRyan EA, Imes S, Wallace C. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes. Diabetes Care. 2004;27(5):1028-32.\u003c/li\u003e\n\u003cli\u003eRetnakaran R, Zinman B. Short-term intensified insulin treatment in type 2 diabetes: long-term effects on \u0026beta;-cell function. Diabetes Obes Metab. 2012;14 Suppl 3:161-6.\u003c/li\u003e\n\u003cli\u003eLeRoith D, Fonseca V, Vinik A. Metabolic memory in diabetes--focus on insulin. Diabetes/metabolism research and reviews. 2005;21(2):85-90.\u003c/li\u003e\n\u003cli\u003eDeFronzo RA. Pathogenesis of type 2 diabetes mellitus. The Medical clinics of North America. 2004;88(4):787-835, ix.\u003c/li\u003e\n\u003cli\u003eKaraca M, Magnan C, Kargar C. Functional pancreatic beta-cell mass: involvement in type 2 diabetes and therapeutic intervention. Diabetes Metab. 2009;35(2):77-84.\u003c/li\u003e\n\u003cli\u003eKahn SE, Zraika S, Utzschneider KM, Hull RL. The beta cell lesion in type 2 diabetes: there has to be a primary functional abnormality. Diabetologia. 2009;52(6):1003-12.\u003c/li\u003e\n\u003cli\u003eFuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, et al. The genetic architecture of type 2 diabetes. Nature. 2016;536(7614):41-7.\u003c/li\u003e\n\u003cli\u003eDeFronzo RA, Soman V, Sherwin RS, Hendler R, Felig P. Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding. The Journal of clinical investigation. 1978;62(1):204-13.\u003c/li\u003e\n\u003cli\u003eKoivisto VA, Yki-J\u0026auml;rvinen H, DeFronzo RA. Physical training and insulin sensitivity. Diabetes/metabolism reviews. 1986;1(4):445-81.\u003c/li\u003e\n\u003cli\u003eGroop L, Lyssenko V. Genes and type 2 diabetes mellitus. Current diabetes reports. 2008;8(3):192-7.\u003c/li\u003e\n\u003cli\u003eDandona P, Chaudhuri A, Mohanty P, Ghanim H. Anti-inflammatory effects of insulin. 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Association between smoking and glycemic control in men with newly diagnosed type 2 diabetes: a retrospective matched cohort study. Annals of medicine. 2022;54(1):1385-94.\u003c/li\u003e\n\u003cli\u003eKaracaer C, Demirci T, Cengiz H, Varim C, Tamer A. The effect of short-term intensive insulin therapy in newly-diagnosed Type-2 diabetic patients. Pak J Med Sci. 2021;37(7):1972-8.\u003c/li\u003e\n\u003cli\u003eKarter AJ. Role of self-monitoring of blood glucose in glycemic control. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2006;12 Suppl 1(0 1):110-7.\u003c/li\u003e\n\u003cli\u003eGarber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2017 EXECUTIVE SUMMARY. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2017;23(2):207-38.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3999987/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3999987/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eOur study aims to compare the efficacy of oral antidiabetic therapy to early insulinization on glycemic control among newly diagnosed type 2 diabetes patients in real-world clinical practice.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort study conducted at a medical center in Taiwan analyzed 1,256 eligible patients from January 2007 to December 2017. Propensity score matching resulted in well-balanced groups of 113 patients each in the oral antidiabetic drug (OAD) and early insulinization cohorts. Glycemic outcomes were assessed in both groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePatients exclusively using OAD showed consistently lower glycated hemoglobin (HbA1c) levels at 3, 12, 24, and 36 months compared to insulin users. At later periods, 78.8% of OAD users achieved glycemic control versus 67.3% of insulin users, with a marginally significant difference. Subgroup analyses suggested a trend favoring well-controlled diabetes in the OAD group, though not statistically significant.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur study finds oral antidiabetic therapy is not inferior to early insulinization for glycemic control in newly diagnosed type 2 diabetes patients, irrespective of initial HbA1c levels. This supports oral therapy as a rational treatment option, even in cases with elevated HbA1c at diagnosis.\u003c/p\u003e","manuscriptTitle":"Oral antidiabetic therapy versus early insulinization on glycemic control in newly diagnosed type 2 diabetes patients: a retrospective matched cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-19 15:12:22","doi":"10.21203/rs.3.rs-3999987/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-06T04:17:36+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"98142301748215403380542326090704458506","date":"2024-05-29T07:07:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-29T00:51:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270716190176831597562373593024023547647","date":"2024-05-25T15:13:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-12T03:07:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"147354673925411141234419699715235601415","date":"2024-05-11T08:01:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-09T07:53:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-08T05:44:04+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-14T08:08:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-14T06:57:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-02-29T13:25:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ca2a5b50-a0c4-48e4-89ee-cb899c4314f9","owner":[],"postedDate":"March 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-07-01T15:21:37+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-19 15:12:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3999987","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3999987","identity":"rs-3999987","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}