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
- Journal
- Obesity pillars (Q1)
- Published
- 14 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Deborah B Horn, Alpana P Shukla, Haocheng Huang, Elvis Twum, Sheryl Elaine Allen, Sanja Giljanovic Kis
- PMID
- 42577069
- DOI
- 10.1016/j.obpill.2026.100301
Why clinicians should know about it
- Picked for Bariatric and Metabolic Surgery (top studies of the week, 16 August 2026): Ranked by evidence level and journal quartile
Abstract
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).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.