Verapamil Could Preserve Beta Cell Function in Newly Diagnosed Type 1 Diabetes

Gregory Forlenza, MD
Courtesy: University of Colorado

Use of verapamil, a calcium channel blocker, could help preserve beta cell function in children and adolescents with newly diagnosed type 1 diabetes (T1D), according to the results of the CLVer trial.

Results of the study, which included 88 people with stage 3 T1D aged 7-17 years, indicate those randomized to verapamil had a C-peptide level 30% greater than their counterparts who received placebo therapy at the end of the 52-week study.

“Once-daily oral verapamil started within 31 days after diagnosis of T1D slowed beta cell decline over 52 weeks in children and adolescents aged 7 years to 17 years,” wrote investigators.

Named the Hybrid Closed Loop Therapy and Verapamil for Beta Cell Preservation in New Onset Type 1 Diabetes (CLVer) trial, the current study was launched with the intent of investigating whether use of verapamil could aid in the preservation of pancreatic beta cell function among younger people with T1D. With this in mind, the trial was designed as a double-blind, randomized clinical trial of children aged 7-17 years who weighed 30 kg or more from 6 pediatric diabetes centers in the US.

The overall trial had a factorial design with each participant randomly assigned to the verapamil group or the placebo group and also to receive either intensive diabetes management with an automated insulin delivery system or standard care diabetes management. The current research pertains specifically to cohorts of 47 patients randomized to verapamil and 41 patients randomized to placebo therapy.

Investigators pointed out an extended-release formulation of verapamil was used in the study. Per trial protocol, drug dose was dependent on each participant’s weight and was started with 60 mg/d or 120 mg/d, with the dose escalated at 2- to 4-week intervals to a maximum of dose of 360 mg/d for participants weighing more than 50 kg.

The overall population of interest in the current study had a mean age of 12.7 (SD, 2.4) years, 41% were female, and the mean time from diagnosis to randomization was 24 (SD, 4) days. Overall, 94% completed the trial.

The primary outcome of interest for the study was area under the curve values for C-peptide level stimulated by a mixed-meal tolerance test at 52 weeks from diagnosis of T1D.

Upon analysis, results indicated the mean C-peptide area under the curve was 0.66 pmol/mL at baseline and 0.65 pmol/mL at 52 weeks among the verapamil group compared with 0.60 pmol/mL at baseline and 0.44 pmol/mL at 52 weeks in the placebo group (adjusted between-group difference, 0.14 pmol/mL [95%CI, 0.01 to 0.27 pmol/mL]; P=.04). Investigators pointed out this difference correlates to a 30% higher C-peptide level at 52 weeks with verapamil.

Further analysis demonstrated a greater proportion of participants in the verapamil group had a peak C-peptide level of 0.2 pmol/mL or greater, with such a level present in 95% of patients in the verapamil group compared with 71% in the placebo group. Analysis of secondary endpoints indicated the adjusted between-group difference for HbA1c at 52 weeks was -0.3% (95% CI, −1.0 to 0.4) in favor of the verapamil group and nonserious adverse events were observed among 17% and 20% of the verapamil group and placebo groups, respectively.

“In children and adolescents with newly diagnosed type 1 diabetes, verapamil partially preserved stimulated C-peptide secretion at 52 weeks from diagnosis compared with placebo,” wrote investigators in their conclusion. “Further studies are needed to determine the longitudinal durability of C-peptide improvement and the optimal length of therapy.”

References

1. Forlenza GP, McVean J, Beck RW, et al. Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA. 2023;329(12):990-999. doi:10.1001/jama.2023.2064