One receptor, big effect
Semaglutide is a once-weekly GLP-1 receptor agonist — it mimics a gut hormone that signals fullness and slows how fast your stomach empties. At the diabetes dose it's sold as Ozempic; at the higher obesity dose, as Wegovy.
It was the drug that turned "GLP-1" into a household word and kicked off the current wave of weight-loss medicine.
How big the effect is
In STEP 8 (JAMA, 2022) — a head-to-head trial — semaglutide 2.4 mg produced 15.8% average weight loss over 68 weeks, versus 6.4% for the older daily drug liraglutide. About 71% of people on semaglutide lost at least 10% of their body weight, compared with 26%.
Gastrointestinal side effects were common in both groups — the familiar trade-off of the class.
Stopping reverses it
STEP 4 (JAMA, 2021) tested withdrawal directly. After an initial run-in, people who kept taking semaglutide lost roughly another 8%, while those switched to placebo regained about 7%.
It's the pattern every GLP-1 shares: the drug manages appetite while you take it — it doesn't permanently reset it.
A landmark drug with rigorous evidence behind large, real weight loss. Tirzepatide edged past it on raw numbers, but semaglutide has the longer track record — with the same "stay on it" caveat and common GI side effects.