The antidiabetic agent semaglutide is used to treat poorly controlled type 2 diabetes in conjunction with diet and exercise. It is currently unclear whether the drug leads to weight loss in obese non-diabetic patients.

Obesity is a major public health problem and is linked to undesirable cardiovascular diseases such as dyslipidemia, high blood pressure, type 2 diabetes and increased mortality. While weight management programs generally focus on decreased caloric intake (through diet) and increased energy expenditure (through exercise), maintaining weight loss over time remains a challenge. The glucagon-like peptide-1 analogue semaglutide is approved for the treatment of type 2 diabetes and to reduce the risk of cardiovascular events in patients with concomitant diabetes and cardiovascular disease. But could the drug play a role in weight loss in those without overt diabetes? That was the question asked by a team from the Feinberg School of Medicine at North-Western University, Illinois, who conducted a 68-week, randomized, placebo-controlled study in overweight and obese patients. The study included patients with a body mass index (BMI)> 30 or> 27 in those with one or more weight-related complications, including high blood pressure, dyslipidemia, obstructive sleep apnea, or cardiovascular disease, but not type 2 diabetes. Participants were randomized to receive subcutaneous semaglutide at a dose of 2.4 mg once a week or an appropriate placebo plus lifestyle intervention. The starting dose of semaglutide was 0.25 mg for the first 4 weeks and was increased every 4 weeks so that by week 16 all participants received the target dose (ie 2.4 mg). The lifestyle counseling included individual counseling sessions every 4 weeks to support maintaining a daily deficit of 500 kcal and increased physical activity (150 minutes per week). The co-primary endpoints were percent change in body weight (from baseline) by the end of the study (week 68) and having reached at least 5% or more body weight.

A total of 1961 participants were randomized to semaglutide (1306) or placebo (655) in a ratio of 2: 1. The mean age of those treated with semaglutide was 46 years (73.1% female), of which 64.5% had a BMI between 30 and 40 and 29.3% had a BMI> 40. The most common comorbidities were dyslipidemia (38.2%) and high blood pressure (36.1%). Semaglutide patients were seen to lose weight from week 4, and by the end of the study, 69.1% of the participants assigned to the drug had lost between 10-15% of their original body weight and 32% had lost more than 20%. This compared with 12% and 1.7% in the patients given placebo. The mean weight loss among those taking semaglutide was -14.9% versus -2.4% with placebo (p <0.001). The semaglutide group also saw greater improvements in cardiovascular risk factors compared to placebo. The most common side effects were gastrointestinal (typically nausea, diarrhea, and vomiting) and were more common in those given semaglutide, although these were generally mild to moderate and resolved with continued treatment. However, more patients taking semaglutide stopped treatment because of side effects (4.5% versus 0.8%).

In their conclusion, the authors reported that semaglutide caused significant and sustained weight loss in patients without type 2 diabetes.

Wilding JPH et al. Semaglutide once a week in overweight or obese adults. New Eng J Med 2021