Verapamil partially preserves C-peptide levels among youths with type 1 diabetes
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Key takeaways:
- Young people with new type 1 diabetes had higher C-peptide area under the curve at 52 weeks with verapamil vs. placebo.
- Residual beta-cell function helps control hyperglycemia and reduces risk for hypoglycemia.
Once-daily oral verapamil may help preserve stimulated C-peptide secretion for children and adolescents with type 1 diabetes, according to a study published in JAMA.
In findings from a randomized, double-blind, placebo-controlled trial, people aged 7 to 17 years with newly diagnosed type 1 diabetes had a higher C-peptide area under the curve at 52 weeks if they received oral verapamil daily vs. placebo. Additionally, 95% of those randomly assigned to verapamil had a C-peptide level of more than 0.2 pmol/L at 52 weeks compared with 71% of participants in the placebo group.
“This finding of a beneficial effect of verapamil has important clinical implications,” Roy W. Beck, MD, PhD, president and medical director of the Jaeb Center for Health Research Foundation in Tampa, Florida, told Healio. “Currently, outside of clinical trials, there are no treatments being prescribed to try to preserve beta cells in newly diagnosed type 1 diabetes. Maintenance of even modest residual beta-cell function helps a person with type 1 diabetes better control hyperglycemia, and importantly, it reduces the risk of hypoglycemia. Higher C-peptide levels also are associated with lower risk of diabetes-related vascular complications and, therefore, is a desirable goal.”
Beck and colleagues conducted a randomized, double-blind clinical trial at six pediatric diabetes centers in the U.S. Children and adolescents aged 7 to 17 years diagnosed with type 1 diabetes within 31 days of randomization who had at least one positive islet autoantibody and had a body weight of 30 kg or more were enrolled. Using a balanced factorial design, the cohort was randomly assigned to verapamil or placebo, as well as to intensive diabetes management with an automated insulin delivery system or standard care for 52 weeks. Verapamil dose was dependent on each participant’s weight and began at 60 mg or 120 mg daily. Dosage increased at 2- to 4-week intervals to a maximum of 360 mg daily for participants weighing more than 50 kg. Visits were conducted 6 weeks after randomization and at 13, 26, 39 and 52 weeks from type 1 diabetes diagnosis. Follow-up visits were conducted 6 weeks after randomization and at 13, 26, 39 and 52 weeks. Blood samples were collected at randomization and every visit except 6 weeks after randomization. A 2-hour mixed-meal tolerance test was performed at each visit. The primary outcome was C-peptide AUC at 52 weeks. Secondary outcomes included peak C-peptide level, the proportion of participants with a peak C-peptide of 0.2 pmol/mL or higher, HbA1c and continuous glucose monitoring metrics.
Higher C-peptide at 52 weeks with verapamil
There were 88 participants in the trial (mean age, 12.7 years; 41% girls; 90% white), of whom 47 received verapamil and 41 received placebo. Mean starting dose was 1.7 mg/kg daily for both groups. The mean ending dose was 5.8 mg/kg daily for the verapamil group and 6.3 mg/kg daily for the placebo group. Drug adherence was 94% with verapamil and 93% with placebo.
At 52 weeks, the verapamil group had a 0.6 pmol/mL mean C-peptide AUC compared with 0.44 pmol/mL for placebo (adjusted treatment difference, 0.14 pmol/mL; 95% CI, 0.01-0.27; P = .04).
Mean peak C-peptide was 0.83 pmol/mL with verapamil vs. 0.55 pmol/mL with placebo. Decreases in HbA1c and time in range between 70 mg/dL and 180 mg/dL at 52 weeks were similar between the groups. There was no between-group difference in change in total insulin dose. The study findings were similar regardless of whether participants were randomly assigned intensive diabetes management or standard care.
Adverse events similar in both groups
Adverse events were reported by 83% of the verapamil group and 73% of the placebo group. There was one severe hypoglycemia event in each group and one diabetic ketoacidosis event in the placebo group. Three participants in each group experienced adverse events unrelated to treatment. The percentage of participants who experienced a nonserious adverse event related to treatment was 17% in the verapamil group and 20% in the placebo group.
Beck said the findings should encourage providers to prescribe verapamil for youths with newly diagnosed type 1 diabetes and potentially for people with longer duration type 1 diabetes whose pancreas is still producing some insulin.
“As with many studies, the results answer one question but raise many other questions that will need to be addressed in future studies, such as should verapamil treatment be continued long term beyond 1 year from diagnosis as long as the patient has residual C-peptide present, will a beneficial effect be present if verapamil therapy is initiated months or even years after type 1 diabetes diagnosis assuming that residual C-peptide is still present and would verapamil treatment be beneficial if initiated at even earlier subclinical stages of type 1 diabetes,” Beck said. “These studies need to be done by either our group or others to better understand the beneficial effects of verapamil in type 1 diabetes.”
For more information:
Roy W. Beck, MD, PhD, can be reached at rbeck@jaeb.org.
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