Mechanism of action
Semaglutide is a selective GLP-1 receptor agonist. Tirzepatide is a dual agonist of both GLP-1 and GIP receptors. GIP — glucose-dependent insulinotropic polypeptide — adds a second satiety signal and contributes to the more pronounced weight effect observed in trials.
Efficacy in trials
SURMOUNT-1, published in the New England Journal of Medicine, measured tirzepatide 15 mg at 72 weeks: mean total body weight loss of approximately 22.5%. STEP-1 measured semaglutide 2.4 mg at 68 weeks: approximately 14.9%. SURMOUNT-5 directly compared the two and produced consistent results in tirzepatide's favor.
Dosing
Both titrate over roughly 16–20 weeks. Semaglutide steps from 0.25 mg to 2.4 mg as defined in the FDA Wegovy prescribing information. Tirzepatide steps from 2.5 mg to 15 mg, with 5 mg, 7.5 mg, 10 mg, and 12.5 mg in between.
Which to choose
For most patients prioritizing maximum weight loss, tirzepatide has the stronger data. For patients with established cardiovascular disease, semaglutide currently has the stronger cardiovascular outcomes data from the SELECT trial. Insurance coverage, supply, and tolerability often dominate the practical decision.