Head to head
Semaglutide vs Tirzepatide
The only pair in the catalog with a head-to-head trial.
Both are once-weekly incretin drugs approved for obesity and type 2 diabetes. Tirzepatide adds GIP agonism to GLP-1 and, in the one direct comparison, produced more weight loss. Semaglutide has the cardiovascular-outcomes trial in obesity that tirzepatide still lacks.
| Measure | SemaglutideGLP-1 receptor agonist | TirzepatideGIP / GLP-1 dual receptor agonist |
|---|---|---|
| Best evidence | Established | Established |
| Human-tested claims | 2 of 2 | 1 of 1 |
| Status | Approved | Approved |
| Cited sources | 4 | 3 |
Where the evidence lands
On weight, the question is settled in tirzepatide's favour: an open-label but randomized 72-week trial put the gap at roughly six and a half percentage points. On what matters beyond the scale, semaglutide is ahead, because SELECT showed a cut in heart attacks, strokes and cardiovascular death in people with obesity and no diabetes, and tirzepatide has no equivalent result yet. Pick by the outcome you care about, not by which is newer.
Where they differ
Each row cites a fixed record. Numbers from different trials are not directly comparable, and the rows say so where that applies.
| Aspect | Semaglutide | Tirzepatide |
|---|---|---|
| Receptors[1] | GLP-1 receptor agonist. | Dual GIP and GLP-1 receptor agonist. |
| Head-to-head weight loss[2] | Mean 13.7% body-weight loss at 72 weeks on the maximum tolerated dose. | Mean 20.2% at 72 weeks in the same trial (SURMOUNT-5, open-label, no diabetes). |
| Cardiovascular outcomes[3] | About 20% fewer major adverse cardiovascular events in obesity without diabetes (SELECT). | No completed cardiovascular-outcomes trial in obesity at the time of review. |
| Approvals[1] | Type 2 diabetes, chronic weight management, cardiovascular risk reduction. | Type 2 diabetes, chronic weight management, obstructive sleep apnea in obesity. |
| Safety profile[1] | Gastrointestinal effects dominate; class boxed warning for thyroid C-cell tumours. | The same gastrointestinal profile and the same class boxed warning. |
What each is studied for
The efficacy claims from each monograph, with their tiers. Follow the entry for sources and safety.
Semaglutide
- EstablishedProduced ~14.9% mean body-weight loss vs ~2.4% on placebo over 68 weeks in adults with obesity (STEP 1).
- EstablishedCut major adverse cardiovascular events by ~20% in patients with cardiovascular disease and obesity but not diabetes (SELECT).
Tirzepatide
- EstablishedProduced ~20.9% mean body-weight reduction at 72 weeks on the top dose vs ~3.1% on placebo (SURMOUNT-1).
Frequently asked
Is tirzepatide just a stronger semaglutide?
Not quite. It is a different molecule acting on two receptors, and it did produce more weight loss in a direct comparison. But semaglutide carries the only cardiovascular-outcomes result in obesity, so the two are ahead on different questions.
Was the head-to-head trial blinded?
No. SURMOUNT-5 was open-label, which is a real limitation for a weight endpoint. The size of the gap makes it unlikely to be an artefact, but it should be read with that in mind.
References
The monographs
- SemaglutideEstablished
GLP-1 receptor agonist
The molecule that rewrote what weight loss looks like.
2 of 2 claims human-tested · 4 references · FDA-approved
- TirzepatideEstablished
GIP / GLP-1 dual receptor agonist
Two incretin receptors, one injection, up to ~21% body weight gone.
1 of 1 claims human-tested · 3 references · FDA-approved
Written by Twenty Residues editorial. Medical review: pending; a named reviewer is being assigned.
Last updated October 1, 2026.
Tiers are explained in the Standard. Spot an error? Report a correction.