Once-Weekly Semaglutide in Adults with Overweight or Obesity

This phase 3, double-blind randomized trial (STEP 1) evaluated once-weekly subcutaneous semaglutide (2.4 mg) versus placebo in 1961 adults with overweight or obesity (BMI ≥30 or ≥27 with ≥1 comorbidity), without diabetes. Participants received 68 weeks of treatment alongside lifestyle intervention. Semaglutide produced a mean 14.9% weight reduction from baseline compared to 2.4% with placebo (difference: −12.4 percentage points; P<0.001). At week 68, ≥5%, ≥10%, and ≥15% weight loss occurred in 86.4%, 69.1%, and 50.5% of the semaglutide group, respectively. Improvements were also noted in waist circumference (−13.54 cm vs. −4.13 cm), blood pressure, glycemic markers, lipid profiles, and quality-of-life scores. Gastrointestinal events (nausea, diarrhea) were common but generally mild and transient. Discontinuation due to GI symptoms was more frequent with semaglutide (4.5% vs. 0.8%). The study concluded that semaglutide plus lifestyle therapy offers substantial and sustained weight loss, with favorable cardiometabolic effects and an acceptable safety profile in this population.

This phase 3, double-blind randomized trial (STEP 1) evaluated once-weekly subcutaneous semaglutide (2.4 mg) versus placebo in 1961 adults with overweight or obesity (BMI ≥30 or ≥27 with ≥1 comorbidity), without diabetes. Participants received 68 weeks of treatment alongside lifestyle intervention. Semaglutide produced a mean 14.9% weight reduction from baseline compared to 2.4% with placebo (difference: −12.4 percentage points; P<0.001). At week 68, ≥5%, ≥10%, and ≥15% weight loss occurred in 86.4%, 69.1%, and 50.5% of the semaglutide group, respectively. Improvements were also noted in waist circumference (−13.54 cm vs. −4.13 cm), blood pressure, glycemic markers, lipid profiles, and quality-of-life scores. Gastrointestinal events (nausea, diarrhea) were common but generally mild and transient. Discontinuation due to GI symptoms was more frequent with semaglutide (4.5% vs. 0.8%). The study concluded that semaglutide plus lifestyle therapy offers substantial and sustained weight loss, with favorable cardiometabolic effects and an acceptable safety profile in this population.