Study Shows Clinical Benefit With Once Weekly Semaglutide in Patients With Obesity

A recent study published in The New England Journal of Medicine reported that treatment with once weekly semaglutide, along with lifestyle intervention, in individuals who are overweight or obese resulted in sustained and clinically beneficial weight loss.

Obesity is a chronic disease that can lead to insulin resistance, hypertension, and dyslipidemia and is associated with type 2 diabetes and cardiovascular disease (CVD), among other conditions. Despite the prevalence of obesity worldwide, there remain few drugs indicated for the disease.

Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved to treat type 2 diabetes and to reduce the risk of cardiovascular events in individuals with type 2 diabetes and CVD.

The double-bind trial included 1961 participants with a body-mass index (BMI) of 30 or greater or 27 in participants with at least 1 weight-related coexisting condition who did not have diabetes. Investigators randomly assigned participants in a 2:1 ratio to either 68 weeks of treatment with once-weekly subcutaneous semaglutide at a 2.4-mg dose or placebo, in combination with a lifestyle intervention.

Data showed that the mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group and -2.4% in the placebo group, demonstrating an estimated treatment difference of -12.4 percentage points (95% CI, -13.4 to -11.5; P0.001).

Eighty-six percent (1047) of individuals in the semaglutide group achieved weight loss of 5% or more, compared with 31.5% (182) of participants receiving placebo, according to the investigators. Those who received semaglutide also more readily saw weight reductions of 10% or more than the placebo group: 838 (69.1%) and 69 (12.0%), respectively. For weight reductions of 15% or more, the semaglutide group reported that 612 (50.5%) achieved the weight loss measure, whereas only 28 (4.9%) in the placebo group achieved the same.

Study authors explained that by losing 5% or more of baseline body weight, participants displayed clinically meaningful responses. Weight loss of 10% to 15% or more is recommended in individuals with many complications from being overweight or obese - including prediabetes, hypertension, and obstructive sleep apnea . Therefore, the study results depict a clear clinical benefit.

Analysis of the data determined that semaglutide led to greater reduction in fat mass than lean body mass in those with obesity and in those with type 2 diabetes, which is on par with previous studies. 

Safety data were consistent with past studies as well. The most frequently reported adverse events (AEs) were mild-to-moderate gastrointestinal disorders; more participants receiving semaglutide than placebo stopped treatment due to AEs.

“Our trial showed that among adults with overweight or obesity (without diabetes), once-weekly subcutaneous semaglutide plus lifestyle intervention was associated with substantial, sustained, clinically relevant mean weight loss of 14.9%, with 86% of participants attaining at least 5% weight loss,” the study authors concluded.

Reference

1. Wilding JP, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine; February 10, 2021. Accessed February 18, 2021. doi: 10.1056/NEJMoa2032183.