Chih-Yuan WangKuo-Chin HuangChia-Wen LuChih-Hsun ChuChien-Ning HuangHarn-Shen ChenI-Te LeeJung-Fu ChenChing-Chu ChenChung-Sen ChenChang-Hsun HsiehKai-Jen TienHung-Yu ChienYu-Yao HuangJui-Pao HsuGuang-Tzuu ShaneAi-Ching ChangYen-Chieh WuWayne Huey-Herng Sheu2026-02-022026-02-022022-08-0210.1210/clinem/dgac436https://scholars.csmu.edu.tw/handle/123456789/4489<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Context</jats:title> <jats:p>There is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic β-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of β-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>This randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Participants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>A total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (−0.36, P = 0.0373) and 450 mg/day (−0.45, P = 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-β score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Addition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.</jats:p> </jats:sec>[SDGs]SDG3journal-article