A new analysis to be presented at this year's European Congress on Obesity (ECO 2026, Istanbul, Turkey, 12-15 May) examined daily oral orforglipron treatment for the treatment of obesity, with or without diabetes, in users aged 65 years and over, with results and a safety profile similar to that seen in the ATTAIN clinical trial programme population. Lead author for this post-hoc analysis is Dr Deborah Horn, Director of the Center for Obesity Medicine and Metabolic Performance at McGovern Medical School at UTHealth Houston, Houston, Texas, USA, and colleagues.
Limited clinical data exist on the use of incretin-based obesity management medications in older adults with or without type 2 diabetes (T2D), and a lack of specific analyses related to older users could be a factor that could make providers or patients in this age group hesitant when considering therapy choices.
Orforglipron is a novel small-molecule, non-peptide, oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) developed by Eli-Lilly and Company (Lilly), who sponsored these analyses. The drug was approved by the US Food and Drug Administration for chronic weight management on April 1, 2026.
Orforglipron demonstrated significant weight reduction vs. placebo in the phase 3, randomised, double-blind, multinational ATTAIN-1 and ATTAIN-2 clinical trials in participants with obesity or obesity and T2D, respectively. In this new analysis of those trials, the authors evaluated efficacy and safety of orforglipron versus placebo in a sub-group of participants aged 65 years and older from ATTAIN-1 and ATTAIN-2.
The ATTAIN-1 and ATTAIN-2 global clinical trials evaluated once-daily orforglipron 6 mg, 12 mg, or 36 mg vs. placebo as an adjunct to healthy diet and physical activity in participants from 9 and 10 countries, respectively. In this sub-group analysis, efficacy outcomes were analysed separately for each trial, and safety data were pooled. The primary endpoint was percent change in body weight from baseline to week 72.
In ATTAIN-1 and ATTAIN-2, 616 randomised participants were ≥65 years of age (n=196 and 420, respectively). Of those, 613 received treatment (orforglipron 6 mg, n=118; 12 mg, n=135; 36 mg, n=146; placebo, n=214). And 79.1% of ATTAIN-1 and 86.2% of ATTAIN-2 participants had hypertension as a comorbidity.
At Week 72, the percent change in weight from baseline in users aged 65 and over in ATTAIN-1 (participants with obesity and without T2D) was –7.9%, –11.3%, and –13.0% with orforglipron 6 mg, 12 mg, and 36 mg, respectively, vs. –1.6% with placebo, all statistically significant findings. Similar results were found for those users aged 65 years and over with T2D and obesity in ATTAIN-2: orforglipron 6 mg: –7.5%; 12 mg: –8.3%; 36 mg: –12.2%; placebo: –2.3% again with all results statistically significant.
Participants with T2D experienced reductions from baseline in glycated haemoglobin (HbA1c – a measure of blood sugar control) of –1.5%, –1.6%, and –1.7% with 6 mg, 12 mg, and 36 mg orforglipron, respectively, vs. –0.1% with placebo. BMI, waist circumference, triglycerides, non-HDL cholesterol, and health-related quality of life also improved in orforglipron vs. placebo treatment groups in participants with or without T2D.
These weight loss results for participants aged 65 years and older were consistent with those seen in the overall trial populations in ATTAIN-1 and ATTAIN-2.
Treatment discontinuations due to adverse events (AEs) were higher for orforglipron (12.3%) vs. placebo (5.5%). The most common AEs with orforglipron were gastrointestinal (64.7% vs. 37.5% for placebo), and were mostly mild or moderate in severity, consistent with other trials featuring GLP-1 medications. There was no statistically significant difference in the occurrence of treatment-emergent AEs possibly related to loss of muscle mass, such as fractures (orforglipron, 6.6%; placebo, 4.3%), treatment-emergent renal events (orforglipron, 3.5%; placebo, 2.6%;), or adjudication-confirmed major adverse cardiovascular events (orforglipron, 3.0%; placebo, 2.3%). Six deaths were reported (orforglipron, 3; placebo, 3) – with no deaths related to the treatment.
The authors say: "In adults aged 65 years and over with overweight or obesity with or without T2D, once-daily orforglipron was associated with significantly greater reductions in body weight and blood sugar markers compared with placebo at Week 72. The adverse event profile in older adults was generally consistent with the overall populations from the ATTAIN-1 and 2 trials, and other trials of GLP-1 medications."
Dr Horn adds: "These data from ATTAIN-1 and ATTAIN-2 participants aged 65 years and older support what we have seen in previous trials with older individuals like the SELECT cardiovascular outcome trial with semaglutide. 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. In short, age should not be a barrier to considering orforglipron."
