Introduction and Objective: Orforglipron (OFG), a once-daily oral non-peptide GLP-1 receptor agonist, was investigated for weight management in the ATTAIN-1 trial. This post-hoc analysis assessed changes in insulin sensitivity (IS) and beta-cell function with OFG in participants with obesity and with or without prediabetes at baseline. Methods: ATTAIN-1 was a randomized, double-blind, phase 3 trial of OFG vs placebo (PBO) in adults with obesity or overweight with ≥1 weight-related comorbidity (excluding type 2 diabetes). A total of 3127 participants were randomized to OFG (6, 12, or 36 mg) or PBO for 72-week treatment. Using the mixed model for repeated measures (MMRM) method, this post-hoc subgroup analysis assessed change from baseline (CFB) in Matsuda index and percent CFB in HOMA2-IR and HOMA2-B at week 72. Results: At week 72, OFG was associated with statistically significant increases from baseline in Matsuda index and statistically significant decreases from baseline in HOMA2-IR among participants in both the prediabetes and normoglycemia cohorts (Table 1). Additionally, treatment with OFG was associated with statistically significant increases from baseline in HOMA2-B in both groups. Conclusion: In this post-hoc analysis, OFG was associated with improvements in measures of IS and beta-cell function in people with obesity or overweight regardless of prediabetes status. Disclosure C. Wysham: Advisory Panel; Current; Abbott Diabetes. Speaker's Bureau; Current; Abbott Diabetes. Research Support; Ended; AbbVie Inc., Bayer AG, Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Eli Lilly and Company. Research Support; Ended; Eli Lilly and Company. Speaker's Bureau; Current; Eli Lilly and Company. Stock/Shareholder; Current; Pendulum. Speaker's Bureau; Ended; MannKind Corporation. M. Davies: Advisory Panel; Current; AbbVie Inc., Amgen Inc., Biomea Fusion, Roche Pharmaceuticals, Regeneron Pharmaceuticals Inc., Daewoong Pharmaceutical. Other - Advisory Panel and Speaker Bureau; Current; Sanofi. Advisory Panel; Current; Zealand Pharma A/S, GlaxoSmithKline plc. Other - Advisory Panel, Speaker Bureau, Grants in support of Trials; Current; AstraZeneca. Other - Consultant/Advisor/Speaker Bureau/Grants in support of Trials; Current; Boehringer Ingelheim International GmbH. Other - Consultant/Advisor/Speaker Bureau; Current; Eli Lilly and Company. Other - Consultant/Advisor/Speaker Bureau/Grants in support of Trials; Current; Novo Nordisk. Speaker's Bureau; Current; Zuellig Pharma Holdings Pte. Ltd. Advisory Panel; Current; EktaH. C. Lee: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. L. Garcia: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. A. Stefanski: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. Y. Wang: Employee; Current; Eli Lilly and Company. B. Behrend: None.
WYSHAM et al. (Fri,) studied this question.