ECO 2026
GLP-1 weight loss holds up in patients 65 and older
Clinical Takeaway: Age alone should not be a reason to withhold GLP-1 therapy in patients with obesity. Older adults appear to benefit similarly to younger ones, with attention to GI tolerability and existing comorbidities.
Older adults make up a growing share of patients with obesity in many high-income countries, but they have been underrepresented in GLP-1 trials. Two new analyses presented at the European Congress on Obesity asked whether the efficacy and safety seen in pivotal trials hold up in patients 65 and older. Both did, with margins close to what was reported in the broader trial populations.
In patients 65 and older in a pooled analysis of six STEP trials, once-weekly semaglutide 2.4 mg produced an average 15.4% weight loss at 68 weeks, compared with 5.1% on placebo. About two-thirds lost at least 10% of body weight, and roughly 1 in 4 moved into a healthy BMI range. Blood pressure, triglycerides, and C-reactive protein all improved meaningfully more with semaglutide than with placebo.
The newly approved oral GLP-1 orforglipron produced dose-dependent weight loss in the over-65 subgroup of the ATTAIN-1 and ATTAIN-2 trials. At the highest dose, patients without diabetes lost about 13% of body weight at 72 weeks; patients with type 2 diabetes lost about 12%, with HbA1c dropping 1.5% to 1.7% across doses. Lipids, waist circumference, and quality-of-life measures also improved.
Critically, efficacy in older adults closely tracked the overall trial populations, suggesting GLP-1 benefit does not diminish with age. The semaglutide analysis included 358 patients 65 and older from a total of 4,523; the orforglipron analysis included 616 of roughly 4,740. In both, the over-65 group was mostly aged 65 to 74, with limited representation over 75.
Both analyses were sponsored by the manufacturers (Novo Nordisk and Eli Lilly) and have not yet undergone full peer review.
Safety profiles in older adults were broadly consistent with younger patients, though some differences emerged. With semaglutide, overall adverse events in the 65+ group were similar to placebo, but serious adverse events were higher (19.0% versus 12.7%); constipation and dizziness were more frequent. Fracture and hypoglycemia rates were comparable.
With orforglipron, treatment discontinuations due to adverse events in older patients were more than double those on placebo (12.3% versus 5.5%), driven mostly by gastrointestinal effects. Serious events, cardiovascular events, and events potentially related to muscle loss were more common in older patients than younger ones, but the pattern held across both treatment and placebo groups, consistent with higher baseline risk. Lean mass accounts for roughly a quarter to a third of weight lost on GLP-1 drugs, a particular concern in older patients already at risk for age-related muscle loss.
“Individuals aged 65 years and older can consider GLP-1 therapy with their health care provider given safety profiles are similar to the broader population and acknowledging that they may also have other health issues that need to be monitored as they initiate and continue GLP-1 therapy,” said Deborah Horn, DO, MPH, director of the Center for Obesity Medicine and Metabolic Performance at McGovern Medical School at UTHealth Houston, whose comments echoed conclusions from the semaglutide analysis. “In short, age should not be a barrier to considering orforglipron.”
Sources: Busetto L. ECO 2026. Abstract 1681. Efficacy and Safety of Semaglutide in Individuals Aged 65 Years and Older: A Pooled Analysis of the STEP Trials. Horn DB. ECO 2026. Abstract 1705. Orforglipron for Obesity Treatment in Older Patients 65 Years and Older With or Without Type 2 Diabetes