A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes.

Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE

Publication: 2017- : New York : Oxford University Press
Original Publication: Springfield, Ill. : Charles C. Thomas

Diabetes Mellitus, Type 2* ; Hypoglycemia*/chemically induced ; Metformin*; Blood Glucose ; Double-Blind Method ; Drug Therapy, Combination ; Glycated Hemoglobin/analysis ; Humans ; Hypoglycemic Agents/adverse effects ; Insulin/therapeutic use ; Treatment Outcome ; Verapamil/therapeutic use

Context: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

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Keywords: HbA1c; R-form verapamil; antidiabetic drug; metformin; type 2 diabetes

ClinicalTrials.gov NCT03317028

0 (Blood Glucose)
0 (Glycated Hemoglobin A)
0 (Hypoglycemic Agents)
0 (Insulin)
9100L32L2N (Metformin)
CJ0O37KU29 (Verapamil)

Date Created: 20220802 Date Completed: 20220929 Latest Revision: 20221207

20231215

PMC9516171

10.1210/clinem/dgac436

35917580