Semaglutide delivered dramatic weight loss and health benefits in adults over 65, offering new hope for healthier aging.
A new analysis of data from the STEP clinical trial program suggests that semaglutide remains both effective and generally safe for older adults living with obesity. The research, conducted by Prof. Luca Busetto of the University of Padova in Italy and colleagues, including researchers from semaglutide manufacturer Novo Nordisk, found that adults aged 65 and older experienced benefits comparable to those seen in the overall trial populations.
Older adults with obesity are often considered a particularly vulnerable group because they frequently have multiple health conditions, greater frailty, and a higher risk of adverse events (AEs). Despite the growing use of glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide, relatively little information has been available about how these medications perform specifically in people over age 65. To address that gap, researchers examined the safety and effectiveness of once-weekly semaglutide 2.4 mg injections in this age group.
Analysis Combined Data From Multiple STEP Trials
The study pooled results from the STEP 1, 3, 4, 5, 8, and 9 trials. It focused exclusively on participants with overweight or obesity who did not have diabetes (because weight loss in obesity drug trials is always lower in people with diabetes than without – thus results cannot be compared or mixed).
Participants were at least 65 years old and had either a BMI of 30 kg/m2 or higher, or a BMI of at least 27 kg/m2 with at least one obesity-related complication (without diabetes). They were randomly assigned to receive either semaglutide 2.4 mg or a placebo.
All participants received lifestyle counseling, and those enrolled in STEP 3 also underwent intensive behavioral therapy. Researchers tracked outcomes over 68 weeks, measuring changes in body weight, waist circumference, waist-to-height ratio (WHtR), BMI category, and several cardiometabolic risk factors, including blood sugar measures, blood pressure, blood lipids, and hs-CRP. They also monitored adverse events (AEs).
Among the 4,523 people enrolled across the selected trials, 358 participants (8%) were at least 65 years old and were included in this analysis. Of those, 248 received semaglutide and 110 received placebo. Most participants (90%) were between 65 and 74 years old, while the remainder were 75 or older.
At the start of the study, the average participant was 69 years old, weighed 99.0 kg, had a BMI of 36.6 kg/m2, and a waist circumference of 115 cm. Women accounted for 72% of participants.
Significant Weight Loss and Waist Reduction
After 68 weeks, participants receiving semaglutide lost an average of 15.4% of their body weight, compared with 5.1% in the placebo group. Waist circumference decreased by an average of 14.3 cm with semaglutide, versus 6.0 cm with placebo.
The proportion of participants achieving substantial weight loss was also much higher with semaglutide. At least 10% weight loss was achieved by 66.5% of semaglutide-treated participants compared with 15.5% of those receiving placebo. At least 15% weight loss was achieved by 46.8% versus 6.4%, while at least 20% weight loss was achieved by 28.6% versus 2.7%.
More Participants Reached a Healthy Weight Range
Researchers also found improvements in body composition measures. A WHtR <0.53 was achieved by 11.3% of participants receiving semaglutide compared with 4.5% of those receiving placebo.
Participants taking semaglutide were more likely to move into lower BMI categories during the study period than those receiving placebo. By week 68, 27.0% of semaglutide-treated participants had reached a BMI of <27 kg/m2 (so-called healthy weight), compared with 5.5% in the placebo group.
The percentages of participants classified as overweight and obesity class I, II, and III all declined in the semaglutide group as more individuals moved into the healthy weight category.
When researchers looked at participants who achieved both a BMI of 27 or less and a WHtR of <0.53, the proportions were 10.5% in the semaglutide group and 2.7% in the placebo group.
Improvements in Heart and Metabolic Health
Semaglutide was also associated with greater improvements in cardiometabolic health markers than placebo (see Table full abstract). Benefits were seen across several measures, including blood pressure, blood fats, cholesterol, and glycated hemoglobin (HbA1c – a measure of blood sugar control used in the diagnosis of diabetes).
Safety Findings in Older Adults
Overall rates of adverse events were similar between the two groups, affecting 89.1% of participants receiving semaglutide and 84.5% of those receiving placebo. Serious adverse events occurred more frequently among semaglutide users, however, with rates of 19.0% compared with 12.7% in the placebo group.
Constipation and dizziness, both known side effects of this class of medication, were reported more often among participants taking semaglutide. Rates of fractures and hypoglycemia were similar between groups and remained below 1% in both.
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 program.”
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.”
Meeting: European Congress on Obesity 2026 (ECO2026)
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