Verapamil and beta cell function in adults with recent-onset type 1 diabetes

• Published in: Nature medicine Vol. 24; no. 8; pp. 1108 - 1112
• Main Authors: Ovalle, Fernando, Grimes, Tiffany, Xu, Guanlan, Patel, Anish J, Grayson, Truman B, Thielen, Lance A, Li, Peng, Shalev, Anath
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.08.2018
• Subjects: Adult; Adults; Antihypertensives; Beta cells; Blood Pressure - drug effects; Calcium; Calcium channels; Clinical trials; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - physiopathology; Glucose; Heart Rate - drug effects; Humans; Insulin; Insulin - metabolism; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - pathology; Pancreas; Pathogenesis; Proteins; Thioredoxin; Verapamil; Verapamil - pharmacology; Verapamil - therapeutic use
• DOI: 10.1038/s41591-018-0089-4
• ISSN: 1078-8956

Pancreatic beta cell loss is a key factor in the pathogenesis of type 1 diabetes (T1D), but therapies to halt this process are lacking. We previously reported that the approved antihypertensive calcium-channel blocker verapamil, by decreasing the expression of thioredoxin-interacting protein, promotes the survival of insulin-producing beta cells and reverses diabetes in mouse models . To translate these findings into humans, we conducted a randomized double-blind placebo-controlled phase 2 clinical trial ( NCT02372253 ) to assess the efficacy and safety of oral verapamil added for 12 months to a standard insulin regimen in adult subjects with recent-onset T1D. Verapamil treatment, compared with placebo was well tolerated and associated with an improved mixed-meal-stimulated C-peptide area under the curve, a measure of endogenous beta cell function, at 3 and 12 months (prespecified primary endpoint), as well as with a lower increase in insulin requirements, fewer hypoglycemic events and on-target glycemic control (secondary endpoints). Thus, addition of once-daily oral verapamil may be a safe and effective novel approach to promote endogenous beta cell function and reduce insulin requirements and hypoglycemic episodes in adult individuals with recent-onset T1D.