Orforglipron reduced body weight versus placebo in adults aged 65 years or older with obesity or overweight in ATTAIN-1 and ATTAIN-2.
Eli Lilly reported a post hoc subgroup analysis of the phase 3 ATTAIN-1 and ATTAIN-2 clinical trials suggesting once-daily oral
“Weight management in older adults requires careful consideration of both benefit and risk. These data are reassuring on both fronts — up to 13% weight loss was observed in patients 65 and older taking Foundayo, with a safety profile similar to what was observed in the broader trial populations,” Rachel Batterham, MD, senior vice president of medical innovation and external engagement at Lilly Cardiometabolic Health, said in the company announcement.1
Key Facts
The analysis, presented at the 33rd European Congress on Obesity in Istanbul, examined outcomes by age subgroup in ATTAIN-1 and ATTAIN-2. In ATTAIN-1, which enrolled adults with obesity or overweight without type 2 diabetes, participants aged 65 years or older receiving orforglipron had mean body weight reductions of 7.9% with 5.5 mg, 11.3% with 9 mg, and 13.0% with 17.2 mg, compared with 1.6% with placebo at week 72.1,2 Among adults younger than 65 years, mean reductions were 7.7%, 9.2%, and 12.4%, respectively, compared with 0.8% with placebo.1
In ATTAIN-2, which enrolled adults with obesity or overweight and type 2 diabetes, participants aged 65 years or older had mean body weight reductions of 7.5% with 5.5 mg, 8.3% with 9 mg, and 12.2% with 17.2 mg, compared with 2.3% with placebo.1,3 Corresponding reductions among adults younger than 65 years were 5.0%, 7.6%, and 9.9%, compared with 2.2% with placebo.1 Lilly reported statistical significance vs placebo across all 3 dose groups in adults aged 65 years or older in both trials.
ATTAIN-1 was a 72-week, randomized, double-blind, placebo-controlled phase 3 trial that enrolled 3127 adults with obesity or overweight, including 195 participants aged 65 years or older.1,2 ATTAIN-2 used a similar 72-week randomized, double-blind, placebo-controlled design and enrolled 1613 adults with obesity or overweight and type 2 diabetes, including 418 participants aged 65 years or older.1,3 Participants in both trials received once-daily orforglipron or placebo with diet and physical activity guidance. The primary endpoint was percent change in body weight from baseline to week 72.
Orforglipron is a small-molecule, nonpeptide glucagon-like peptide-1 receptor agonist. Unlike oral semaglutide, which has specific administration requirements, Lilly states orforglipron can be taken once daily without food or water restrictions. A pharmacokinetic study cited by the company evaluated the effect of food consumption on orforglipron exposure, safety, and tolerability.4
According to Lilly, Foundayo is FDA-approved in the US for chronic weight management in adults with obesity or in some adults with overweight and at least 1 weight-related comorbidity, as an adjunct to reduced-calorie diet and increased physical activity.1
In the video below, Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss the FDA approval of orforglipron (Foundayo).
Editor’s Note: Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others. Bellini reports disclosures with Abbott Diabetes Care, MannKind, Povention Bio, and others.
For clinicians, the analysis addresses a practical question in obesity pharmacotherapy: whether efficacy and tolerability observed in broader trial populations extend to older adults, who may have sarcopenia risk, polypharmacy, frailty, renal vulnerability, and higher baseline cardiometabolic risk. The magnitude of weight reduction in adults aged 65 years or older appeared broadly similar to that in younger participants in the company-reported analysis, including in the subgroup with type 2 diabetes, where weight loss with incretin-based therapies may be more modest than in individuals without diabetes.
Safety findings were consistent with known GLP-1 receptor agonist effects. Gastrointestinal adverse events—including nausea, constipation, diarrhea, and vomiting—were the most frequently reported events and were sometimes severe.1 Pooled serious adverse events occurred in 9.9%, 13.0%, and 11.6% of adults aged 65 years or older receiving orforglipron 5.5 mg, 9 mg, and 17.2 mg, respectively, compared with 11.4% with placebo. In adults younger than 65 years, serious adverse events occurred in 5.6%, 6.2%, and 5.4% across the same dose groups, compared with 5.4% with placebo.1
Interpretation should remain cautious. The age subgroup analysis was post hoc and exploratory, with fewer older adults than younger adults enrolled, and formal comparisons between age groups were not prespecified. The findings may support use of orforglipron across age groups within its approved indication, but they do not resolve questions about long-term durability, functional outcomes, lean mass preservation, or comparative effectiveness against injectable GLP-1–based therapies in older adults.
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