The mechanism, in plain language
GLP-1 is a hormone your gut releases after eating. Medications like semaglutide mimic it: they slow how quickly your stomach empties and act on appetite centers in the brain, so you feel full sooner and stay full longer. Tirzepatide adds a second hormone pathway (GIP) on top.
The effect is on appetite and fullness, not willpower.
What the trials actually showed
In the STEP 1 trial (published in the New England Journal of Medicine, 2021), adults taking weekly semaglutide 2.4mg lost about 15% of body weight on average over 68 weeks, versus roughly 2% with placebo — both alongside lifestyle support. In SURMOUNT-1 (NEJM, 2022), the highest tirzepatide dose averaged around 20%.
Both trials studied the manufacturers' products (Wegovy, Zepbound). Compounded semaglutide and tirzepatide were not studied in them.
Two caveats live inside those numbers: they're averages, not promises — individual results vary widely — and the trials paired medication with lifestyle changes, not instead of them.
Who shouldn't take them
Per FDA prescribing information, GLP-1 medications carry a boxed warning for medullary thyroid carcinoma — anyone with a personal or family history of it, or of MEN 2 syndrome, shouldn't take them. Pregnancy, a history of pancreatitis, and gastroparesis are also disqualifying or need careful in-person evaluation.
The intake asks about each of these before provider review, and declines when online treatment is not safe.
What to expect if prescribed
Doses start low and step up over weeks to manage the most common side effects — nausea, constipation, fatigue — which usually ease as your body adjusts. Your provider sets the ramp and adjusts it based on how you actually respond.
Sources
- FDA prescribing information: semaglutide (Wegovy), tirzepatide (Zepbound)
- Wilding et al., STEP 1 trial, New England Journal of Medicine (2021)
- Jastreboff et al., SURMOUNT-1 trial, New England Journal of Medicine (2022)
Educational content, not medical advice. Whether any treatment is appropriate for you is a decision made by a licensed provider who has reviewed your health.