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

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, promot...

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Bibliographic Details
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: New York Nature Publishing Group US 01.08.2018
Nature Publishing Group
Subjects:
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Adult
Adults
Antihypertensive agents
Antihypertensives
Beta cells
Biomedical and Life Sciences
Biomedicine
Blood Pressure - drug effects
Calcium
Calcium channels
Cancer Research
Care and treatment
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
Diabetes therapy
Diabetics
Glucose
Health aspects
Heart Rate - drug effects
Humans
Infectious Diseases
Insulin
Insulin - metabolism
Insulin-Secreting Cells - drug effects
Insulin-Secreting Cells - pathology
Letter
Metabolic Diseases
Molecular Medicine
Neurosciences
Pancreas
Pancreatic beta cells
Pathogenesis
Peptides
Proteins
Risk factors
Thioredoxin
Thioredoxins
Type 1 diabetes
Type 2 diabetes
Verapamil
Verapamil - pharmacology
Verapamil - therapeutic use
ISSN:1078-8956, 1546-170X, 1546-170X
Online Access:Get full text
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Description
Summary: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 1 . 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. A phase 2 placebo-controlled randomized trial reveals that verapamil promotes beta cell function in adult subjects with recent-onset type 1 diabetes.
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AUTHOR CONTRIBUTIONS
F.O., T.G. and A.J.P. were responsible for patient care, MMTTs and sample and data collection. G.X., T.B.G. and L.A.T. helped with sample preparation, P.L. provided statistical advice. F.O. and A.S. designed the studies and analyzed the results and A.S. wrote the manuscript. All authors reviewed and approved the manuscript.
Anath Shalev, M.D., Professor and Director, Comprehensive Diabetes Center, University of Alabama at Birmingham, 1825 University Blvd, SHELBY Bldg 1206, Birmingham, AL 35294-2182, Phone: (205) 996-9546, Fax: (205) 996-5220, shalev@uab.edu
ISSN:1078-8956
1546-170X
1546-170X
DOI:10.1038/s41591-018-0089-4