Verapamil and beta cell function in adults with recent-onset type 1 diabetes.
Verapamil and beta cell function in adults with recent-onset type 1 diabetes.
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DOI：
10.1038/s41591-018-0089-4
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发表时间：
2018-08
期刊：
影响因子：
82.9
通讯作者：
Shalev A
中科院分区：
文献类型：
--
作者：
Ovalle F;Grimes T;Xu G;Patel AJ;Grayson TB;Thielen LA;Li P;Shalev A
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.
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DOI：
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