LBP4.170 Orforglipron for Obesity Treatment in Older Patients ≥65 Years With or Without Type 2 Diabetes – Dr Deborah B Horn and colleagues (late breaking poster)
AD19.03 Efficacy and Safety of Semaglutide in Individuals Aged ≥65 Years: A Pooled Analysis of the STEP Trials (Professor Luca Busetto and colleagues, Hall 5, 9:50H AM, Fri 15 May)
New post-hoc analysis examined daily oral orforglipron in adults over 65 with obesity, with or without diabetes
This new analysis 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.”
Conflict of interest statement:
Deborah B. Horn: Consulting fees/honorarium from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Kailera, Novo Nordisk, Roche, and Zealand Pharmaceuticals; institutional research support from Eli Lilly and Company, KVK Tech, Novo Nordisk, and Weight Watchers. Alpana P. Shukla: Institutional research funding from Novo Nordisk, Eli Lilly and Company, and Viking Therapeutics Inc. and serves as a consultant/advisor to Eli Lilly and Company, Novo Nordisk, and Sun Pharmaceuticals.
Haocheng Huang, Elvis Twum, and Sanja Giljanovic Kis: Employees and shareholders of Eli Lilly and Company.
For full abstract, click here
For full poster, click here
Pooled analysis of trails reveals semaglutide shows good efficacy in older adults aged over 65 years
A new analysis of the STEP trails carried out by semaglutide manufacturer Novo Nordisk has analysed various trials to show the safety and efficacy of the obesity drug semaglutide in older adults (over 65 years), and found similar efficacy and safety as in the general trial populations . The study is by Prof Luca Busetto from the University of Padova in Italy and colleagues including from Novo Nordisk, who sponsor this new study.
Individuals of advanced age with obesity represent a vulnerable group, often presenting with comorbidities and frailty, and being at risk of adverse events (AEs). Information on the use of glucagon-like peptide-1 (GLP-1) receptor agonists including semaglutide in this population is limited; therefore, the authors decided assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg in individuals aged 65 years and over.
The analysis pooled together data from the STEP 1, 3, 4, 5, 8 and 9 trials (only in people with obesity or overweight, not diabetes, because weight loss in obesity drug trials is always lower in people with diabetes than without – thus results cannot be compared or mixed). It included participants aged ≥65 years with body mass index of at least 30 kg/m², or at least 27 kg/m² and at least 1 obesity-related complication (without diabetes) who were randomised to receive semaglutide 2.4 mg or placebo. All participants received lifestyle intervention and, in STEP 3, intensive behavioural therapy. Endpoints were assessed from baseline to week 68 and included percentage change in body weight; proportion of participants achieving categorical body weight reductions (≥10%, ≥15%, ≥20%); change in waist circumference; proportion of participants achieving waist to height ratio (WHtR) <0.53; shift in BMI category; and changes in cardiometabolic risk factors (glucose parameters, blood pressure, serum lipids and hs-CRP). Adverse events (AEs) were also assessed.
Of the total population in the selected trials (N=4523), 358 participants (8%) were aged 65 years or older and included in the analysis (semaglutide 2.4 mg, n=248; placebo, n=110), with most (90%) being aged 65–74 years (and the others 75 years and over). Across the pooled semaglutide and placebo groups at baseline, mean age was 69 years, bodyweight was 99.0 kg, BMI was 36.6 kg/m² and waist circumference was 115 cm; 72% were female.
At week 68, there was a mean −15.4% change in body weight for semaglutide 2.4 mg vs −5.1% for placebo, and a mean −14.3 cm vs −6.0 cm change in waist circumference, respectively. Proportions of participants achieving body weight reduction thresholds in the semaglutide 2.4 mg vs placebo groups were 66.5% vs 15.5% (at least 10%), 46.8% vs 6.4% (at least 15%) and 28.6% vs 2.7% (at least 20%), respectively.
In the semaglutide 2.4 mg group, 11.3% achieved a WHtR <0.53, compared with 4.5% with placebo. A greater proportion of semaglutide-treated participants improved their BMI category from baseline to week 68 compared with placebo (see Figure full abstract). A BMI of <27 kg/m² (so called healthy weight) was achieved by 27.0% of participants in the semaglutide group vs 5.5% in the placebo group; and the proportion of elderly patients in the overweight and obesity class I, II and III categories all fell in the semaglutide group at week 68 due to the increase in participants who had reached a healthy weight.
For participants achieving both a BMI of 27 or less and a WHtR of <0.53 these values were 10.5% vs 2.7%, respectively. Greater improvements in cardiometabolic risk factors were observed with semaglutide 2.4 mg vs placebo (see Table full abstract), including blood pressure, blood fats, cholesterol and glycated haemoglobin (HbA1c – a measure of blood sugar control used in diagnosis of diabetes).
Proportions of participants experiencing AEs and serious AEs in the semaglutide 2.4 mg vs placebo groups were similar for AEs overall (89.1% vs 84.5%), but higher for semaglutide re: serious AEs - 19.0% vs 12.7%, respectively. Constipation and dizziness rates (known side effects of this class of drug) were higher with semaglutide, while fractures and hypoglycaemia were comparable to placebo, both affecting less than 1% in each group.
Dr Busetto concludes: “In this analysis of individuals with obesity aged 65 years and older, semaglutide reduced body weight and improved cardiometabolic risk factors compared with placebo, and the safety and efficacy profile of semaglutide was consistent with that reported in the STEP programme.”
He adds: “In many countries, including many high-income countries, the majority of the cases of excess weight actually occur in adults aged 65 years and over, representing a major driver for obesity-related complications and an important cause of reduced quality of life and disability. Our results support the use of semaglutide in this patient group.”
Conflict of interest – the authors list several conflicts of interest, including Dr Busetto, and some authors are also employees of semaglutide manufacturer Novo Nordisk. See full abstract for full details.
For full abstract including figures, click here
