Semaglutide Associated with Substantial Weight Loss in Patients with Obesity

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Adults with obesity who received once-weekly subcutaneous semaglutide, in conjunction with lifestyle management, experienced substantial weight loss vs placebo, according to the recently published Semaglutide Treatment Effect in People with Obesity (STEP) 1 study.

More than half of STEP 1 study participants lost 15% of body weight, study authors reported.

Published February 10, 2021 in The New England Journal of Medicine, the randomized double-blind trial included 1961 adults without diabetes with a body mass index (BMI) of ≥30 kg/m² (≥27 kg/m² in persons with ≥1 weight-related coexisting condition).

Participants were randomly assigned in a 2:1 ratio to 68 weeks of treatment with once-weekly subcutaneous semaglutide 2.4 mg or placebo, plus lifestyle intervention. The lifestyle intervention was comprised of individual counseling sessions from registered dieticians every 4 weeks to help participants adhere to a reduced-calorie diet and more exercise.

The coprimary endpoints were percentage change in body weight and weight reduction of at least 5%. Researchers also used the primary estimand to assess effects regardless of treatment discontinuation or rescue interventions.

Researchers found that mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group vs -2.4% in the placebo group, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5).

Mean weight reduction in the semaglutide group was 15.3 kg vs 2.g kg in the placebo group, for an estimated treatment difference of -12.7 kg (95% CI, -13.7 to -11.7).

Also, at week 68, weight reductions of ≥5% more was significantly greater among participants in the semaglutide group vs placebo (86.4% vs 31.5%), as was weight loss of ≥10% (69.1% vs 12%) and ≥15% (50.5% vs 4.9%; P<.001 for all comparisons).

As is typical with other glucagon-like peptide-1 receptor agonists, the most common adverse events reported with semaglutide was nausea and diarrhea; these were typically transient and mild-to-moderate in severity, added researchers. More participants in the semaglutide group vs placebo group discontinued treatment due to gastrointestinal events (4.5% vs 0.8%).

“This is by far the most effective intervention we have seen for weight management when you compare it to many of the currently existing drugs,” said corresponding author Robert Kushner, MD, professor of medicine and medical education, Northwestern University Feinberg School of Medicine, Chicago, Illinois, in a press release. “Semaglutide sets the bar for a new generation of more effective weight-loss medications.”

It is also important to note the study limitations included the majority of female and White participants, the relatively short study duration, the exclusion of patients with type 2 diabetes, and the potential that participants may represent a subgroup with greater commitment to weight loss vs general population, added authors.