Verapamil Shows Promise as Type 1 Diabetes Treatment

Patients taking the blood pressure medication required less insulin and demonstrated immunomodulatory benefits.

Blood pressure drug verapamil can help patients with type 1 diabetes (T1D) use less insulin while boosting their immune defense, according to new research.

Published in Nature Communications,¹ researchers found that patients taking the oral blood pressure medication not only required less daily insulin 2 years after first diagnosis of the disease, but also showed evidence of immunomodulatory benefits.

These findings are important, said study leader Anath Shalev, MD, Director of the Comprehensive Diabetes Center at the University of Alabama at Birmingham in Birmingham, Alabama, because there are currently no oral medications available for T1D.²

Shalev and colleagues also found that several proinflammatory markers of T follicular helper cells, including CXCR5 and IL-21, were significantly elevated in those with T1D compared healthy controls—changes reversed by verapamil treatment.

“Our results reveal for the first time that verapamil treatment may also affect the immune system and reverse these [T1D]-induced changes,” Shalev said. “This suggests that verapamil, and/or the [T1D] improvements achieved by it, can modulate some circulating proinflammatory cytokines and T helper cell subsets, which in turn may contribute to the overall beneficial effects observed clinically.”

Continuing the medication is necessary, however. In the 2-year study, participants who stopped daily doses of verapamil at 1 year saw their disease at 2 years worsen at rates similar to participants in the control group, the researchers found.

“The fact that these beneficial verapamil effects seemed to persist for two years, whereas discontinuation of verapamil led to disease progression, provides some additional support for its potential usefulness for long-term treatment,” Shalev added.

These new findings stem from more than 2 decades of Shalev’s basic research into a gene in pancreatic islets called TXNIP. In 2014, Shalev’s UAB research lab reported that verapamil completely reversed diabetes in animal models, and she announced plans to test the effects of the drug in a human clinical trial, according to UAB.

In 2018, Shalev and colleagues reported the benefits of verapamil in a 1-year clinical study of patients with T1D, finding that regular oral administration of verapamil enabled patients to produce higher levels of their own insulin, thus limiting their need for injected insulin to regulate blood sugar levels.

Shalev and colleagues caution that their study, with its small number of participants, needs to be confirmed by larger clinical studies, like the current verapamil-T1D study ongoing in Europe.

Still, the preservation of some beta cell function is promising. “In humans with [T1D], even a small amount of preserved endogenous insulin production—as opposed to higher exogenous insulin requirements—has been shown to be associated with improved outcomes and could help improve quality of life and lower the high costs associated with insulin use,” Shalev said.

References

1. 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
2. Hansen J. An oral medication shows benefits treating Type 1 diabetes for at least two years after diagnosis. University of Alabama at Birmingham News. Published March 3, 2022. Accessed March 15, 2022. https://www.uab.edu/news/research/item/12670-an-oral-medication-shows-benefits-treating-type-1-diabetes-for-at-least-two-years-after-diagnosis