A Calcium Channel Blocker With an Exciting New Indication

Diabetes mellitus is chronic global health crisis affecting 37.3 million people in the United States, or approximately 11.3% of the population.¹ Type 1 diabetes (T1D) is an autoimmune-inflammatory process that destroys the insulin-producing pancreatic beta cells. T1D affects 1.6 million people, or about 5.7% of the population with diabetes mellitus.²

Insulin is the sole treatment for individuals with T1D. Currently, no oral therapy is available for the treatment of T1D.

Verapamil is a calcium channel blocker indicated for the treatment of hypertension.³ A small phase 2 randomized, placebo-controlled trial using oral verapamil in patients with new-onset T1D showed verapamil improved beta-cell function by a 2-hour mixed-meal-stimulated C-peptide AUC, with lower insulin requirements, and fewer hypoglycemic events compared to placebo.⁴ No adverse events were noted.

These highly promising results led the investigators to study the underlying mechanisms of verapamil’s effects on T1D. Chromogranin A, a T1D-autoantigen, was normalized by verapamil, and led to decreases in pro-inflammatory markers, promoting an anti-oxidative, anti-apoptotic, and immunomodulatory gene expression profile in human islet cells.⁵ Importantly, chronic use of verapamil was associated with delayed T1D progression and lowered insulin requirements.

This data is truly exciting for this patient population. Even a small amount of preserved insulin production is associated with improved outcomes, including quality of life.

It is too early to suggest this treatment for persons with T1D, however. There is a need for further research to establish what the true benefit and safety profile of verapamil may be in patients with T1D.

References:

1. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States. Centers for Disease Control and Prevention. January 18, 2022. Accessed March 14, 2022. https://www.cdc.gov/diabetes/data/statistics-report/index.html
2. Prevalence of Diagnosed Diabetes. Centers for Disease Control and Prevention. December 29, 2021. Accessed March 14, 2022. https://www.cdc.gov/diabetes/data/statistics-report/diagnosed-diabetes.html
3. Calan SR Verapamil Hydrochloride Sustained-Release Oral Caplets Package Insert. US Food and Drug Administration. Accessed March 14, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019152s041lbl.pdf
4. Ovalle F, Grimes T, Xu G, et al. Verapamil and beta cell function in adults with recent-onset type 1 diabetes. Nat Med. 2018;24:1108-1112. doi:10.1038/s41591-018-0089-4
5. Xu G, Grimes TD, Grayson TB, et al. Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes. Nat Commun. 2022;13(1):1159. doi:10.1038/s41467-022-28826-3