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.
Orforglipron was associated with significant weight loss in older adults with obesity compared to placebo at Week 72, but the clinical relevance of the findings should be carefully considered.
Where it sits
this study against the rest of the orforglipron (ly-3502970) corpusSummary and findings
This study evaluated the effects of orforglipron at doses of 5.5 mg, 9 mg, and 17.2 mg in participants aged ≥65 years with obesity, comparing outcomes to placebo. The primary endpoint was the percent change in body weight from baseline to Week 72. The results indicated significant weight reductions in the orforglipron groups compared to placebo.
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).
Background
This paper addresses the limited research on incretin-based medications for obesity treatment in older adults, particularly those aged 65 and older. Prior studies have primarily focused on younger populations, leaving a gap in understanding the efficacy and safety of such treatments in older adults. This analysis is significant as it provides insights into the effects of orforglipron, a novel GLP-1 receptor agonist, in a demographic that may respond differently to obesity treatments.
Methods
This was a post hoc subgroup analysis of the ATTAIN-1 and ATTAIN-2 trials, involving participants aged ≥65 years. A total of 616 participants were randomized, with 613 receiving treatment: orforglipron 5.5 mg (n=118), 9 mg (n=135), 17.2 mg (n=146), or placebo (n=214). The primary outcome measure was the percent change in body weight from baseline to Week 72, with safety data pooled across the trials.
Results
At Week 72, participants receiving orforglipron experienced significant weight reductions: -7.9% for 5.5 mg, -11.3% for 9 mg, and -13.0% for 17.2 mg, compared to -1.6% for placebo in ATTAIN-1 (all p<0.001). Similar results were observed in ATTAIN-2, with weight changes of -7.5% for 5.5 mg, -8.3% for 9 mg, and -12.2% for 17.2 mg, compared to -2.3% for placebo (all p<0.001). Gastrointestinal adverse events were the most common but generally mild to moderate.
Interpretation
The findings suggest that orforglipron may lead to significant weight loss in older adults, which is consistent with prior literature on GLP-1 receptor agonists. However, while the statistical significance is clear, the clinical significance of the weight changes, particularly for the lower doses, may be limited. The analysis is confounded by its post hoc nature and the relatively small sample sizes for each treatment group, which may affect the robustness of the conclusions drawn.
Key findings
- -7.9% weight change with orforglipron 5.5 mg vs placebo at Week 72, n=118, p<0.001.
- -11.3% weight change with orforglipron 9 mg vs placebo at Week 72, n=135, p<0.001.
- -13.0% weight change with orforglipron 17.2 mg vs placebo at Week 72, n=146, p<0.001.
- -1.6% weight change with placebo at Week 72, n=214, p<0.001.
- -7.5% weight change with orforglipron 5.5 mg in ATTAIN-2 vs placebo, p<0.001.
- -2.3% weight change with placebo in ATTAIN-2, p<0.001.
Limitations
- post hoc analysis may introduce bias
- small sample sizes for each treatment group
- short follow-up duration of 72 weeks
- no long-term safety data reported