The GLP-1 System
Semaglutide works by mimicking a hormone called GLP-1 (glucagon-like peptide-1) — a naturally occurring hormone released by your gut in response to eating. GLP-1 does several things: it tells your pancreas to release insulin, it slows digestion so nutrients absorb more slowly, and critically, it sends satiety signals to your brain. Semaglutide mimics GLP-1 but lasts much longer — the natural hormone degrades in 2 minutes; semaglutide lasts approximately one week.
The STEP Trials: Clinical Evidence
The STEP trial program is the most comprehensive weight loss clinical trial data available for any peptide. In STEP 1, 1,961 adults with obesity received weekly semaglutide 2.4mg or placebo for 68 weeks. The semaglutide group lost an average of 14.9% of body weight; placebo group lost 2.4%. In STEP 4, stopping semaglutide resulted in regaining two-thirds of the lost weight within one year — highlighting the chronic nature of treatment.
Cardiovascular Benefits: The SELECT Trial
In 2023, the SELECT trial published results showing semaglutide 2.4mg reduced major cardiovascular events (heart attack, stroke, cardiovascular death) by 20% in overweight or obese adults without diabetes. This was a landmark finding that expanded semaglutide's evidence base beyond weight loss alone and prompted the FDA to approve this cardiovascular indication.