{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:39:59Z","timestamp":1793450399743,"version":"4.5.0"},"reference-count":25,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2023,3,28]]},"abstract":"Importance<\/jats:title>In preclinical studies, thioredoxin-interacting protein overexpression induces pancreatic beta cell apoptosis and is involved in glucotoxicity-induced beta cell death. Calcium channel blockers reduce these effects and may be beneficial to beta cell preservation in type 1 diabetes.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine the effect of verapamil on pancreatic beta cell function in children and adolescents with newly diagnosed type 1 diabetes.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This double-blind, randomized clinical trial including children and adolescents aged 7 to 17 years with newly diagnosed type 1 diabetes who weighed 30 kg or greater was conducted at 6 centers in the US (randomized participants between July 20, 2020, and October 13, 2021) and follow-up was completed on September 15, 2022.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Participants were randomly assigned 1:1 to once-daily oral verapamil (n\u2009=\u200947) or placebo (n\u2009=\u200941) as part of a factorial design in which participants also were assigned to receive either intensive diabetes management or standard diabetes care.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was area under the curve values for C-peptide level (a measure of pancreatic beta cell function) stimulated by a mixed-meal tolerance test at 52 weeks from diagnosis of type 1 diabetes.<\/jats:p><\/jats:sec>Results<\/jats:title>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. 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<\/jats:italic>\u2009=\u2009.04). 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<\/jats:sub> was 6.6% in the verapamil group vs 6.9% in the placebo group (adjusted between-group difference, \u22120.3% [95% CI, \u22121.0% 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.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>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. Further studies are needed to determine the longitudinal durability of C-peptide improvement and the optimal length of therapy.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04233034<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.2023.2064","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T11:00:28Z","timestamp":1677236428000},"page":"990","source":"Crossref","is-referenced-by-count":173,"title":["Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes"],"prefix":"10.1001","volume":"329","author":[{"given":"Gregory P.","family":"Forlenza","sequence":"first","affiliation":[{"name":"Barbara Davis Center, Anschutz Medical Campus, University of Colorado, Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"McVean","sequence":"additional","affiliation":[{"name":"University of Minnesota, Minneapolis"},{"name":"now with 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