Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes

Nat Commun. 2022 Mar 3;13(1):1159. doi: 10.1038/s41467-022-28826-3.


Currently, no oral medications are available for type 1 diabetes (T1D). While our recent randomized placebo-controlled T1D trial revealed that oral verapamil had short-term beneficial effects, their duration and underlying mechanisms remained elusive. Now, our global T1D serum proteomics analysis identified chromogranin A (CHGA), a T1D-autoantigen, as the top protein altered by verapamil and as a potential therapeutic marker and revealed that verapamil normalizes serum CHGA levels and reverses T1D-induced elevations in circulating proinflammatory T-follicular-helper cell markers. RNA-sequencing further confirmed that verapamil regulates the thioredoxin system and promotes an anti-oxidative, anti-apoptotic and immunomodulatory gene expression profile in human islets. Moreover, continuous use of oral verapamil delayed T1D progression, promoted endogenous beta-cell function and lowered insulin requirements and serum CHGA levels for at least 2 years and these benefits were lost upon discontinuation. Thus, the current studies provide crucial mechanistic and clinical insight into the beneficial effects of verapamil in T1D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Diabetes Mellitus, Type 1*
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunotherapy
  • Insulin
  • Verapamil / pharmacology
  • Verapamil / therapeutic use


  • Immunologic Factors
  • Insulin
  • Verapamil