The study was led by Prof Luca Busetto of the University of Padova in Italy along with colleagues, including researchers from Novo Nordisk, the manufacturer of semaglutide and sponsor of the study.

Semaglutide Examined in Older Adults

Older adults with obesity are often considered medically vulnerable because they frequently have multiple health conditions and greater frailty, which can increase the risk of adverse events (AEs). Researchers say there is still limited information about how glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide perform in this age group.

To better understand the drug’s effects, investigators analyzed data from the STEP 1, 3, 4, 5, 8 and 9 trials. The analysis only included people with obesity or overweight who did not have diabetes because weight loss results in obesity drug trials are typically lower in people with diabetes, making direct comparisons difficult.

Participants were aged ≥65 years and had a body mass index of at least 30 kg/m², or at least 27 kg/m² with at least 1 obesity-related complication (without diabetes). They were randomly assigned to receive either semaglutide 2.4 mg or a placebo. All participants also received lifestyle intervention, while those in STEP 3 additionally received intensive behavioral therapy.

Researchers evaluated outcomes over 68 weeks. These included changes in body weight, waist circumference, waist to height ratio (WHtR), BMI category, and cardiometabolic risk factors such as blood pressure, cholesterol, blood fats, glucose measures and hs-CRP. Adverse events (AEs) were also monitored.

Significant Weight Loss and Health Improvements

Among the total trial population (N=4523), 358 participants were aged 65 or older and included in the analysis. Of those, 248 received semaglutide 2.4 mg and 110 received placebo. Most participants (90%) were between ages 65-74 years, while the remainder were 75 years and older.

At the beginning of the study, the average participant age was 69 years. Average body weight was 99.0 kg, average BMI was 36.6 kg/m², and average waist circumference was 115 cm. Women accounted for 72% of participants.

By week 68, participants receiving semaglutide experienced an average body weight reduction of −15.4%, compared with −5.1% in the placebo group. Waist circumference also dropped more sharply with semaglutide, decreasing by an average of −14.3 cm versus −6.0 cm with placebo.

The percentage of participants achieving major weight loss milestones was also much higher in the semaglutide group. Weight reductions of at least 10% were achieved by 66.5% of semaglutide participants compared with 15.5% receiving placebo. For at least 15% weight loss, the figures were 46.8% versus 6.4%, while 28.6% of semaglutide users lost at least 20% of their body weight compared with 2.7% in the placebo group.

Improvements in BMI and Cardiometabolic Health

Researchers also found notable improvements in waist to height ratio and BMI categories among semaglutide users.

In the semaglutide group, 11.3% achieved a WHtR <0.53, compared with 4.5% in the placebo group. More participants receiving semaglutide also moved into healthier BMI categories over the course of the study (see Figure full abstract).

A BMI of <27 kg/m² (so called healthy weight) was achieved by 27.0% of participants taking semaglutide, compared with 5.5% of those receiving placebo. The proportions of participants classified as overweight or in obesity class I, II and III all declined in the semaglutide group as more individuals reached healthier weight ranges.

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.

The semaglutide group also showed greater improvements in cardiometabolic risk factors (see Table full abstract), including blood pressure, cholesterol, blood fats and glycated haemoglobin (HbA1c – a measure of blood sugar control used in diagnosis of diabetes).

Safety Findings and Side Effects

Overall rates of adverse events (AEs) were similar between groups, affecting 89.1% of semaglutide participants and 84.5% of placebo participants. However, serious adverse events were reported more frequently in the semaglutide group, occurring in 19.0% of participants compared with 12.7% in the placebo group.

Constipation and dizziness, which are known side effects associated with this type of medication, were more common with semaglutide. Rates of fractures and hypoglycemia were similar between groups and affected less than 1% of participants 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 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.”