The only randomised head-to-head between the two molecules, and the number every comparison since has leaned on.
SURMOUNT-5 randomised adults with obesity and without diabetes to tirzepatide or semaglutide and measured them directly: approximately 20% mean body-weight reduction at 72 weeks against approximately 14%. It is the only head-to-head trial between these molecules.
Everything else comparing them is cross-trial, which is weaker evidence because populations, protocols and endpoints differ. When a page quotes a difference without naming SURMOUNT-5, that is what it is doing.
Six percentage points is large but it is a mean, and the distribution matters more to an individual. Semaglutide retains a longer real-world record, more cardiovascular outcome evidence, broader formulary position and an oral formulation.
The practical read: if both are affordable and covered, the head-to-head favours tirzepatide. If only one is covered, coverage wins, because the molecule you can sustain beats the one you abandon.
Sources
- SURMOUNT-5, NCT05822830 — source
Dated 2025-12-04. If this item is out of date or wrong, tell us through contact and the change is logged in corrections.
Primary sources
Clinical, dosing and regulatory statements on this page rest on the documents below. Links go to the publisher, not to a summary of it. Prices are not sourced here — they carry a verification date instead, and the reason is set out in the source ledger.
- ZEPBOUND (tirzepatide) full prescribing information — DailyMed, US National Library of Medicine. Dose ladder, contraindications, warnings, storage.
- FDA’s concerns with unapproved GLP-1 drugs used for weight loss — US Food and Drug Administration. Compounded GLP-1 risks, API import alert, cold-chain complaints.
- FD&C Act provisions that apply to human drug compounding — US Food and Drug Administration. Why a compounded preparation is lawful without being FDA-approved.
- Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1) — N Engl J Med 2022;387:205-216. Registration NCT04184622. The weight-reduction and adverse-event figures used across this site.
- The full source ledger — every primary source, what it supports, the date we read it, and the claims we deliberately do not source.