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ISTANBUL — Adults with obesity aged 65 years or older treated with semaglutide achieved clinically meaningful weight loss and improvements in cardiometabolic risk factors broadly consistent with results seen in the wider STEP clinical trial, according to a new pooled analysis.

The findings help address a key evidence gap around the use of GLP-1 receptor agonists in older adults, often underrepresented in obesity drug trials despite carrying a high burden of obesity-related complications and disability.

“The main result is that the efficacy and safety profile is similar,” said study lead Luca Busetto, MD, professor of internal medicine at the University of Padua in Padua, Italy. “When you treat people aged 65 years and older, you can expect similar results to younger people in terms of weight loss, metabolic improvement, and side effects.”

He noted that in many high-income countries, most obesity cases occur in adults older than 65 years, while obesity trials largely enroll younger adults. “That discrepancy is the reason we performed this post hoc analysis,” he said. “Our results support the use of semaglutide in this patient group.”

Busetto presented the findings here at the 33rd European Congress on Obesity (ECO) 2026.

Clinically Meaningful Weight Loss

Data from six STEP obesity trials were pooled, focusing on 358 adults aged 65 years or older without diabetes (7.9% of total participants). Mean age was 69 years, mean BMI was 36.6, and 72.3% were women. All participants received lifestyle interventions; those in STEP 3 also received intensive behavioral therapy.

By week 68 (approximately 16 months), participants receiving once weekly subcutaneous semaglutide 2.4 mg had a mean body weight reduction of 15.4%, compared with 5.1% in the placebo group. Waist circumference also decreased more with semaglutide than with placebo, by 14.3 cm vs 6.0 cm.

Approximately two thirds (66.5%) of the semaglutide-treated participants achieved ≥ 10% weight loss, compared with 15.5% in the placebo arm. Nearly half achieved ≥ 15% weight loss, and 28.6% achieved ≥ 20% weight reduction, compared with 2.7% with placebo. In addition, 27% of semaglutide-treated participants reached a BMI below 27 by week 68, compared with 5.5% of placebo recipients, while 11.3% achieved a waist to height ratio below 0.53, compared with 4.5% with placebo.

Greater improvements were also seen with semaglutide across several cardiometabolic markers, including blood pressure, lipid levels, fasting glucose parameters, glycated hemoglobin, and high-sensitivity C-reactive protein.

Safety Questions Remain Important in Older Adults

Older adults with obesity can be particularly vulnerable to adverse events because of frailty, multimorbidity, sarcopenia risk, and polypharmacy, noted Busetto.

“Obesity is a chronic disease, and many of the complications of obesity become more important with aging,” Busetto said. “Age and obesity work in parallel, increasing the risk of cardiovascular morbidity, diabetes, mortality, disability, and poor physical performance.”

Overall adverse event rates were high in both the semaglutide (89.1%) and placebo (84.5%) groups. Serious adverse events occurred more frequently with semaglutide than with placebo (19.0% vs 12.7%).

However, investigators said the overall safety profile remained consistent with previous STEP program findings. Known gastrointestinal and neurologic side effects associated with GLP-1 receptor agonists, including constipation and dizziness, were more common with semaglutide. Fracture and hypoglycemia rates were low and comparable between groups.

Busetto acknowledged ongoing concerns around muscle and bone health in older adults receiving antiobesity medications. “Of course, we have concerns about frailty, sarcopenia, muscle mass, and bone health,” he said. “But these trials did not include detailed data on body composition, muscle strength, or physical performance.”

He pointed to emerging evidence suggesting that improvements in function may still occur despite reductions in lean mass. “One small study showed that although muscle mass decreased during weight loss, muscle strength improved,” he said. “Part of the apparent muscle loss may reflect reductions in fat infiltrating the muscle. Physical activity, particularly resistance training, remains important.”

Weight Cycling May Pose Greater Long-Term Risk

Busetto suggested that repeated cycles of weight loss and regain may pose greater risks to older adults than sustained treatment. “‘Weight loss is always accompanied by some muscle loss,” he said. “In older adults, regained weight is more likely to be fat than muscle, and repeated cycles may impair body composition and function.”

Obesity itself is also increasingly recognized as a driver of disability and poorer quality of life in older age, Busetto added, noting that these treatments are not just about weight. Weight loss is important, he said, but obesity should always be viewed within the broader context of chronic disease and complications.

Lean Mass Loss Does Not Always Mean Muscle Dysfunction

Commenting for Medscape News Europe, Louis Aronne, MD, obesity specialist and director of the Comprehensive Weight Control Center at Weill Cornell Medicine, New York City, said concerns about muscle loss during weight reduction in older adults should be viewed in context.

“When people lose weight, we expect some loss of lean mass as well as fat mass,” Aronne said. “But lean mass is not all muscle, it also includes organs and other tissues, so it’s not necessarily as concerning as many people think.”

He noted that emerging evidence suggests muscle function may improve despite reductions in measured lean mass. “Some of the latest data on muscle physiology during weight loss suggest this may not be as big an issue as we once thought,” he said. “Muscle contains fat within it, and some of that fat is reduced during weight loss. So muscle may appear smaller without necessarily worsening function.” 

However, he stressed that preserving muscle remains an important priority, particularly in older adults with sarcopenic obesity. “People losing weight should still focus on preserving muscle mass with adequate protein intake, sufficient calories, and resistance exercise,” Aronne said.

The analysis was funded by Novo Nordisk. Busetto reported receiving consulting and speaker fees from multiple companies including Novo Nordisk, Eli Lilly, Pfizer, Roche, and Regeneron. Two coauthors are employees and shareholders of Novo Nordisk. Aronne reported having financial relationships with all the major pharmaceutical companies involved in the field.