Old Drug Verapamil May Have New Use in Type 1 Diabetes

In children and adolescents with new-onset type 1 diabetes, the calcium channel blocker verapamil slowed the destruction of insulin-producing pancreatic beta cells for up to a year, new data show.

Use of daily verapamil within a month of diagnosis resulted in a 30% increase in C-peptide secretion (a measure of preserved beta-cell function) compared to placebo at 52 weeks, without serious adverse events.

To put it another way, verapamil delayed the expected decline in C-peptide production from 3 months after diagnosis of type 1 diabetes to 6 months after diagnosis.

"We think this is a really, really exciting finding that's hopefully going to impact the care for children with type 1 diabetes in the new-onset period," lead author Gregory P. Forlenza, MD, said during his presentation of the data on February 24 at the annual Advanced Technologies & Treatments for Diabetes (ATTD) meeting.

"In view of the favorable safety profile, particularly by comparison with immune-suppressive agents, once-a-day oral administration, and low cost, initiation of verapamil should be a consideration for newly diagnosed patients with type 1 diabetes," added Forlenza, a pediatric endocrinologist at the Barbara Davis Center for Diabetes, Anschutz Medical Campus, University of Colorado, Aurora.

Asked to comment, Robert A. Gabbay, MD, PhD, chief scientific and medical office, American Diabetes Association, told Medscape Medical News: "This is an exciting preliminary study that suggests that an old medication, verapamil, could have benefit in those newly diagnosed with type 1 diabetes to help preserve beta-cell function and insulin production. We look forward to larger studies to verify these initial reports."

The new data were also simultaneously published in JAMA as part of the CLVer (Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes) trial.

The randomized, double-blind, six-center trial involved 113 participants, aged 7-17 years, with newly diagnosed type 1 diabetes. They were randomized to the most advanced commercially available automated insulin delivery systems available or standard care to test the effects of intensive glucose control on C-peptide levels for 52 weeks during the COVID-19 pandemic (July 2020 to September 2022). Eighty-eight patients who weighed 30 kg (66 lb) or more were further randomized (1:1) to daily extended-release verapamil or placebo for the same duration. 

The positive findings for verapamil, published in one paper, contrasted with the negative ones for the automated insulin delivery (AID) system. The latter did not prevent the expected decline in C-peptide, putting to rest a long-held hypothesis that reducing glucotoxicity might preserve beta-cell function in newly diagnosed individuals with type 1 diabetes, noted Forlenza.

Could Combination Therapy Work?

In recent years, immune-modulating agents have increasingly been shown to preserve beta-cell function in both new-onset and preclinical type 1 diabetes. One such agent, teplizumab (Tzield, Provention Bio), was approved by the US Food and Drug Administration in November 2022 to delay type 1 diabetes onset in those at high risk.

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