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


ABSTRACT: 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 models1. 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.

SUBMITTER: Ovalle F 

PROVIDER: S-EPMC6092963 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Ovalle Fernando F   Grimes Tiffany T   Xu Guanlan G   Patel Anish J AJ   Grayson Truman B TB   Thielen Lance A LA   Li Peng P   Shalev Anath A  

Nature medicine 20180709 8


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<sup>1</sup>. To translate these findings into humans, we conducted a randomized double-blind placebo-controlled ph  ...[more]

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