229-OR: Orforglipron Improves Markers of Beta-Cell Function and Insulin Sensitivity in Type 2 Diabetes

• DOI: 10.2337/db24-229-or
• Publication Date: 2024-07-19T14:45:24Z
• Authors: JULIO ROSENSTOCK; DEBORAH A. ROBINS; KEVIN L. DUFFIN; JONATHAN M. WILSON; KIEREN J. MATHER; HIYA BANERJEE; YANZHU LIN; SARAH EYDE; CHRISTOF M. KAZDA; MANIGE KONIG
• Keywords: BETA (programming language)

Orforglipron (OFG), an oral, non-peptide GLP-1 receptor agonist, demonstrated significantly greater glycemic control and weight loss at doses ≥12 mg vs placebo (PBO) or dulaglutide (DU) 1.5 in a 26-week phase 2 study of adults with type diabetes (T2D) (Table). These exploratory analyses investigated mechanisms by which OFG improved T2D analyzing biomarkers. Participants (mean age, 58.9 years; baseline HbA1c, 8.1%; weight, 100.3 kg) treated diet exercise, with/without metformin, were randomized to PBO, DU mg, once-daily 3, 12, 24, 36, 45 mg. Biomarkers β-cell function insulin sensitivity analyzed mixed model repeated measures, excluding data after drug discontinuation rescue initiation. 26 weeks from HOMA-B increased PBO DU. HOMA-IR (computed insulin) decreased ≥24 but was not different Fasting glucose-adjusted glucagon suggest may be partly explained sensitivity. Additional studies are ongoing understand these mechanisms. Disclosure J. Rosenstock: Research Support; Biomea Fusion, Inc. Other Relationship; Lilly Diabetes. Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Corcept Therapeutics. Novo Nordisk. Pfizer Sanofi, Boehringer-Ingelheim. Shionogi Ltd. Structure Therapeutics, Advisory Panel; Terns Pharmaceuticals, Zealand Pharma A/S. Applied Hanmi Pharm. Ltd., Oramed Pharmaceuticals. Scholar Rock. D.A. Robins: None. K.L. Duffin: Employee; Eli Company. J.M. Wilson: K.J. Mather: H. Banerjee: Y. Lin: Stock/Shareholder; Company, AstraZeneca. S. Eyde: C.M. Kazda: M. Konig: Funding Company