1716-P: Menopausal Stage and Weight Outcomes with Orforglipron vs. Placebo: Post Hoc Subgroup Analysis from ATTAIN-1 and ATTAIN-2

Introduction and Objective: Obesity, a chronic progressive disease, is exacerbated by estrogen deficiency during menopause. Orforglipron (OFG), an oral small-molecule, non-peptide GLP-1 receptor agonist, has demonstrated significant body weight (BW) reductions in ATTAIN-1 and -2. This post-hoc analysis evaluates OFG’s effect on BW in women by menopausal stage. Methods: Female participants with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with ≥1 obesity related complication in ATTAIN-1 and -2 were analyzed by menopausal status: pre-, peri-, or post-menopause. BW, waist circumference (WC), waist-to-height ratio (WtHR) changes and the proportion achieving BW reduction thresholds (≥5%, ≥10%, ≥15%, ≥20%) vs placebo were assessed at 72 weeks using the efficacy estimand. Results: Significant reductions in BW of up to 14% and WC 11 cm were observed across subgroups with OFG vs PBO (p0.001) for both studies. With OFG, up to 83% achieved ≥5% BW reduction vs 23% with PBO. Significantly higher proportions of participants taking OFG achieved BW reduction threshold vs PBO (p0.001). More OFG-treated participants moved to lower Waist-to-Height Ratio categories than PBO. Conclusion: OFG treatment in women with obesity or overweight, irrespective of menopausal stage, resulted in significant BW and WC reductions vs PBO. These findings underscore OFG’s efficacy in managing obesity across different menopausal stages. Disclosure A. Ciudin: Advisory Panel; Current; Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim International GmbH. Consultant; Ended; AstraZeneca. B. Tchang: Advisory Panel; Current; Novo Nordisk, Roman Health Ventures, Skye Bioscience, Amgen Inc., Lilly, Pfizer Inc., Boehringer Ingelheim International GmbH. A.J. Balmain: Employee; Current; Eli Lilly and Company. S. Klise: Employee; Current; Eli Lilly and Company. D. Mojdami: Employee; Current; Eli Lilly and Company. W. Ye: Employee; Current; Eli Lilly and Company. X. Mi: None. H.T. Hoffmann: Employee; Current; Eli Lilly and Company.