Nature Medicine: Published on November, 2022

Obesity is a chronic, relapsing disease with a substantial morbidity, mortality, and healthcare burden. Drug interventions for the treatment of obesity provide a potential valuable adjunct to lifestyle interventions, which often achieve only limited weight loss that is difficult to maintain.

Semaglutide, a glucagon-like peptide-1 analog, is an antidiabetic medication that is approved for chronic weight management in adults with obesity or overweight with at least one weight-related condition based on results from the Semaglutide Treatment Effect in People with Obesity (STEP) clinical trial program.

TAKE-HOME MESSAGE

This placebo-controlled randomized STEP 5 trial investigated the efficacy and safety of once-weekly subcutaneous of 2.4-mg semaglutide administration as long-term treatment in adults with obesity or in those who are overweight with at least one weight-related comorbidity (excluding diabetes).

At 104 weeks, treatment with semaglutide was associated with a −15.2% mean change in body weight (treatment difference, −12.6% points) and a significantly higher likelihood of achieving weight loss ≥5% from baseline compared with placebo.

With respect to cardiometabolic risk factors, semaglutide treatment improved a range of parameters, including waist circumference, blood pressure, HbA1c levels, and lipid levels, as well as reducing fasting insulin and glucose, which may represent an increase in insulin sensitivity.

Safety and tolerability were consistent with adverse events seen with this drug class, with no new safety signals. However, mild to moderate gastrointestinal adverse events were more frequent with semaglutide.

This study suggests that semaglutide is a safe and effective treatment for patients who are overweight and obese, promoting sustained weight loss over a 2-year period.

The take-home message from this STEP 5 clinical trial is that weight loss occurs and is sustainable at least up to 2 years with semaglutide in persons who are overweight without diabetes with one or more comorbidity or in persons with obesity without diabetes.