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Tight Glycemic Control, Verapamil in Newly Diagnosed Pediatric Type 1 Diabetes

The effects of tight glycemic control and verapamil on pancreatic beta-cell function are explored in children and adolescents newly diagnosed with type 1 diabetes.

Glycemic Control Study: Excellent glucose control was achieved through intensive diabetes management that included automated insulin delivery in a study at 6 U.S. centers, but the decline in pancreatic C-peptide secretion at 52 weeks was not affected. Results based on a primary outcome of mixed-meal tolerance test–stimulated C-peptide area under the curve (a measure of pancreatic beta cell function) 52 weeks from diagnosis showed the following: “Among 113 participants (mean [SD] age, 11.8 [2.8] years; 49 females [43%]; mean [SD] time from diagnosis to randomization, 24 [5] days), 108 (96%) completed the trial. The mean C-peptide area under the curve decreased from 0.57 pmol/mL at baseline to 0.45 pmol/mL at 52 weeks in the intensive management group, and from 0.60 to 0.50 pmol/mL in the standard care group (treatment group difference, −0.01 [95% CI, −0.11 to 0.10]; P = .89). The mean time in the target range of 70 to 180 mg/dL, measured with continuous glucose monitoring, at 52 weeks was 78% in the intensive management group vs 64% in the standard care group (adjusted difference, 16% [95% CI, 10% to 22%]). One severe hypoglycemia event and 1 diabetic ketoacidosis event occurred in each group.”

Verapamil Study: More favorable results were achieved with verapamil, which partially preserved stimulated C-peptide secretion at 52 weeks from diagnosis compared with placebo in children and adolescents with newly diagnosed type 1 diabetes. “Among 88 participants (mean age, 12.7 [SD, 2.4] years; 36 were female [41%]; and the mean time from diagnosis to randomization was 24 [SD, 4] days), 83 (94%) completed the trial,” the researchers report. “In the verapamil group, the mean C-peptide area under the curve was 0.66 pmol/mL at baseline and 0.65 pmol/mL at 52 weeks 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). This equates to a 30% higher C-peptide level at 52 weeks with verapamil. The percentage of participants with a 52-week peak C-peptide level of 0.2 pmol/mL or greater was 95% (41 of 43 participants) in the verapamil group vs 71% (27 of 38 participants) in the placebo group. At 52 weeks, hemoglobin A1c was 6.6% in the verapamil group vs 6.9% in the placebo group (adjusted between-group difference, −0.3% [95% CI, −1.0% to 0.4%]). Eight participants (17%) in the verapamil group and 8 participants (20%) in the placebo group had a nonserious adverse event considered to be related to treatment.”

Editorial: “Several questions and opportunities are now presented,” an editorialist writes. “A well-tolerated, inexpensive, oral treatment such as verapamil with modest benefits on C-peptide production is relevant to practice because even stimulated C-peptide levels of 0.2 pmol/mL or greater are associated with a substantial reduction in the risk of retinopathy and nephropathy. Does the effect of verapamil persist off treatment as it does for some immunomodulation therapies in patients with recent-onset type 1 diabetes? The post hoc analysis may identify clinical, metabolic, and immunological baseline characteristics that differentiate responders from nonresponders. Verapamil’s distinct action on the beta cell may, in combination with promising immunomodulatory and immunosuppressive agents, provide better preservation of beta cell function.”

Source: JAMA