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

Nature Medicine volume 24, pages 1108–1112 (2018)Cite this article

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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.

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Fig. 1: Screening, randomization and treatment.
Fig. 2: Effects of verapamil on endogenous beta cell function.
Fig. 3: Effects of verapamil on glycemic control and insulin requirements.
Fig. 4: Blood pressure and heart rate throughout the trial.

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Acknowledgements

The work was supported by JDRF grant 3-SRA-2014-302-M-R to A.S. The UAB Physiology Core was supported by DRC P30DK079626, and the UAB Center for Clinical and Translational Science was supported by UL1TR001417. We thank M. Preuss for excellent administrative support during the study.

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Authors and Affiliations

  1. Comprehensive Diabetes Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Fernando Ovalle, Tiffany Grimes, Guanlan Xu, Anish J. Patel, Truman B. Grayson, Lance A. Thielen & Anath Shalev

  2. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

    Peng Li

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  1. Fernando Ovalle
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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. A.S. wrote the manuscript. All authors reviewed and approved the manuscript.

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Correspondence to Anath Shalev.

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The authors declare no competing interests.

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Ovalle, F., Grimes, T., Xu, G. et al. Verapamil and beta cell function in adults with recent-onset type 1 diabetes. Nat Med 24, 1108–1112 (2018). https://doi.org/10.1038/s41591-018-0089-4

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