GLP-1 receptor agonistsGLP-1 agonists · Incretin medicines
Prescription medicines that mimic the GLP-1 satiety signal for far longer.
GLP-1 receptor agonists are prescription only medicines that activate the GLP-1 receptor, mimicking the natural gut hormone but lasting long enough to act over days rather than minutes. Some newer agents are dual agonists, also acting at the GIP receptor.
The trial results are large by the standards of weight management research. In a 68 week randomised trial of once weekly semaglutide, mean body weight fell by about 14.9% against 2.4% on placebo; in a 72 week trial of tirzepatide the highest dose group lost about 20.9% against 3.1%. Both were run alongside lifestyle support.
They work by reducing intake rather than by raising expenditure. Appetite falls, the stomach empties more slowly, and people eat less, which is a mechanism worth stating plainly because it removes the mystique.
Two findings shape how they should be used. A meaningful share of the weight lost is lean mass, broadly in line with what any large energy deficit does, which makes protein intake and resistance training more important during treatment rather than less. And weight returns after stopping: in the STEP 1 extension, participants regained about two thirds of their lost weight in the year after withdrawal, with cardiometabolic improvements drifting back too.
That regain reframes what these medicines are. They manage an ongoing condition rather than delivering a cure, which the marketing rarely leads with.
Gastrointestinal side effects are common and are the usual reason for stopping. Prescribing, monitoring and dose decisions belong with a clinician, and this site does not cover dosing.
In practice, if you are taking one, the questions worth attention are protein, resistance training and what happens afterwards.
Sources
- Efficacy and Safety of Once-Weekly Subcutaneous Semaglutide in Adults With Overweight or Obesity (STEP 1, 68 weeks)
- Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med 2022;387:205-216
- Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab 2022;24:1553-1564