SC semaglutide, if given continuously for two years, maintains weight loss in obese adults: STEP 5 trial

The study, published in the journal Nature Medicine, found that once-weekly subcutaneous semaglutide, when given to adults with overweight or obesity along with behavioral intervention, led to a clinically impactful and sustained weight loss of 15.2% at week 104. Also, it led to improvements in weight-related cardiometabolic risk factors.

The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity or overweight with at least one weight-related comorbidity without diabetes.

Behavioral intervention, including physical activity and diet modifications, is the cornerstone for treating overweight and obesity. However, because behavioral intervention does not result in clinically meaningful and sustainable weight loss, pharmacotherapy is needed as an additional tool for the long-term management of weight in people with a body mass index (BMI) of at least 30 kg m–2 or at least 27 kg m–2 in those with weight-related comorbidities.

Semaglutide is a glucagon-like peptide-1 (GLP-1) analog that got approval for treating type 2 diabetes (subcutaneous semaglutide and oral semaglutide) and for reducing cardiovascular events risk in patients with type 2 diabetes and cardiovascular disease (subcutaneous semaglutide only).

Based on the STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial, subcutaneous semaglutide at a dose of 2.4 mg once weekly was approved in Europe, the United States, and Canada, and the United Kingdom for weight management in overweight or obese adults.

Against the above background, W. Timothy Garvey, the University of Alabama at Birmingham, Birmingham, AL, USA, and the team assessed the safety and efficacy of once-weekly subcutaneous semaglutide 2.4 mg compared to placebo (both given in conjunction with behavioral intervention) for long-term treatment of overweight/obese adults with at least one weight-related comorbidity, without diabetes.

Body weight change and weight loss achievement of ≥5% at week 104 were measured (co-primary endpoints). The efficacy assessment was done in all randomized participants independent of treatment discontinuation or rescue intervention.

The study included 304 participants randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152) from 5 October 2018 to 1 February 2019, out of which 92.8% completed the trial. Most participants were females (77.6%), with a mean age of 47.3 years, body mass index of 38.5 kg m–2, and weight of 106.0 kg.

The study demonstrated the following findings:

• The mean change in body weight from baseline to week 104 was −15.2% in the semaglutide group (n = 152) versus −2.6% with placebo (n = 152), for an estimated treatment difference of −12.6 %-points.
• More participants in the semaglutide group than in the placebo group achieved weight loss ≥5% from baseline at week 104 (77.1% versus 34.4%).
• Gastrointestinal adverse events, primarily mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%).

"The study results showed that in adults with overweight (with at least one weight-related comorbidity) or obesity (without diabetes), treatment with semaglutide led to substantial, sustained weight loss over 104 weeks versus placebo," the researchers concluded.

Reference:

Garvey, W.T., Batterham, R.L., Bhatta, M. et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med 28, 2083–2091 (2022). https://doi.org/10.1038/s41591-022-02026-4