Orforglipron for obesity treatment in older patients ≥65 years with or without type 2 diabetes: A post hoc subgroup analysis of the ATTAIN-1 and ATTAIN-2 trials.

BACKGROUND: Limited studies exist on incretin-based medications in older adults with obesity. Orforglipron, a novel small-molecule, non-peptide, oral glucagon-like peptide-1 receptor agonist (GLP-1 RA), led to significant weight reduction in the Phase 3, randomized, double-blind ATTAIN-1 and ATTAIN-2 trials in participants with obesity or obesity and type 2 diabetes, respectively. METHODS: This post hoc subgroup analysis evaluated once-daily orforglipron 5.5 mg, 9 mg, or 17.2 mg vs. placebo as an adjunct to healthy diet and physical activity among participants aged ≥65 years. Efficacy outcomes were analyzed separately for each trial, and safety data were pooled. The primary endpoint was percent change in body weight from baseline to Week 72. RESULTS: In ATTAIN-1 and ATTAIN-2, 616 randomized participants were ≥65 years of age. Of those, 613 received treatment (orforglipron 5.5 mg, n = 118; 9 mg, n = 135; 17.2 mg, n = 146; placebo, n = 214). At Week 72, the percent change in weight from baseline among participants from ATTAIN-1 was -7.9% (95% CI: -10.0, -5.9), -11.3% (-13.4, -9.3), and -13.0% (-15.7, -10.4) with orforglipron 5.5 mg, 9 mg, and 17.2 mg, respectively, vs. -1.6% (-3.2, 0.1) with placebo (all p < 0.001), which was similar for those in ATTAIN-2 (orforglipron 5.5 mg: -7.5% [-9.1, -5.9]; 9 mg: -8.3% [-9.7, -6.8]; 17.2 mg: -12.2% [-13.9, -10.6]; placebo: -2.3% [-3.1, -1.4]; all p < 0.001). Comparable findings were observed in participants <65 years of age. Gastrointestinal adverse events with orforglipron were most common and generally mild to moderate in severity. CONCLUSION: In this post hoc analysis of adults ≥65 years of age with obesity with or without type 2 diabetes, once-daily orforglipron was associated with significantly greater reductions in body weight vs. placebo at Week 72. The safety profile was generally consistent with other GLP-1 RAs. (ATTAIN-1: NCT05869903; ATTAIN-2: NCT05872620).