Semaglutide

The STEP-1 trial randomized 1,961 adults with body mass index ≥30 (or ≥27 with weight-related comorbidities and without diabetes) to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks, alongside lifestyle intervention. Mean change in body weight was -14.9% in the semaglutide arm versus -2.4% in placebo. Secondary endpoints — including weight reduction ≥5%, ≥10%, and ≥15% — favored semaglutide with high statistical significance. Adverse events were predominantly gastrointestinal and consistent with the known GLP-1 receptor agonist class profile.

Researchers ran a large 68-week study comparing weekly semaglutide injections to placebo in nearly 2,000 adults with overweight or obesity (without diabetes). On average, the semaglutide group lost about 15% of their starting body weight; the placebo group lost about 2%. The most common side effects were stomach-related (nausea, diarrhea), which is typical for this class of molecule.

SUSTAIN-6 was a randomized, double-blind cardiovascular outcomes trial in 3,297 patients with type 2 diabetes at high cardiovascular risk. Participants received subcutaneous semaglutide (0.5 mg or 1.0 mg once weekly) or placebo for a median 2.1 years. The primary composite outcome — cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke — occurred in 6.6% of the semaglutide group versus 8.9% of placebo (HR 0.74, 95% CI 0.58–0.95, p<0.001 for non-inferiority; p=0.02 for superiority). Hemoglobin A1c reductions and body-weight reductions were also significantly greater with semaglutide.

A multi-year study followed about 3,300 people with type 2 diabetes who were at high risk of heart disease. Half received semaglutide injections; half received placebo. People on semaglutide had fewer cardiovascular events (heart attacks, strokes, cardiovascular deaths) than those on placebo. They also had better blood sugar control and lost more weight.