Long-term effectiveness on glycemic control of insulin compared to combined oral antidiabetic drugs for initial intensive treatment in newly diagnosed type 2 diabetes: A duplicated target trial

Abstract

Although both intensive insulin therapy (IIT) and combined oral antidiabetic drugs (COAD) can achieve initial intensive glycemic control, evidence comparing their long-term effectiveness following initial remission remains limited. Therefore, this study aims to compare long-term glycemic control and the risk of drug-free remission failure between IIT and COAD in patients who successfully achieved initial intensive glycemic control. This duplicated target trial utilized a cohort of 60, 736 patients with type 2 diabetes from 3 hospitals in South Korea (2001–2024). Patients treated with insulin were assigned to the IIT group, and those receiving metformin combined with other oral antidiabetic drugs to the COAD group. Successful initial intensive treatment was defined as HbA1c <7.0% following treatment cessation. Failure of drug-free glycemic remission was defined as HbA1c ≥7.0% during follow-up. After 1:1 propensity score matching, Cox proportional hazard model was employed to evaluate the risk of remission failure between groups, estimating adjusted hazard ratios (aHRs) with 95% confidence intervals. Among 2092 patients achieving successful initial intensive treatment, each group assigned 355 following 1:1 propensity score matching (IIT group: mean age, 64.56 [standard deviation, 13.16] years; 49.0% female; COAD group: mean age, 64.08 [standard deviation, 12.90] years; 45.6% female). Baseline mean HbA1c and fasting plasma glucose were 6.26% and 115.4mg/dL in the IIT group, and 6.31% and 126.4mg/dL in the COAD group. During follow-up, HbA1c and body weight diverged significantly, with higher levels observed in the COAD group. The IIT group indicated a significant lower risk of drug-free glycemic remission failure compared to the COAD group (aHR, 0.47 [95% confidence interval, 0.31–0.73]). In patients with newly diagnosed type 2 diabetes achieving successful initial intensive treatment, IIT was associated with better long-term glycemic control compared with COAD, despite treatment discontinuation. © 2026 the Author(s). Published by Wolters Kluwer Health, Inc.