Semaglutide vs tirzepatide
They were compared directly, over 72 weeks, in 751 people. Tirzepatide won on weight by 6.5 percentage points. Semaglutide still has one thing tirzepatide does not.
Key takeaways
- They were compared head to head. SURMOUNT-5 randomised 751 adults with obesity and no diabetes to tirzepatide or semaglutide for 72 weeks.
- Tirzepatide won on weight: 20.2% mean body weight reduction against 13.7% for semaglutide.
- Semaglutide has something tirzepatide does not: a completed cardiovascular outcomes trial, SELECT, showing fewer heart attacks, strokes and cardiovascular deaths.
- Gastrointestinal side effects caused more people to stop semaglutide (5.6%) than tirzepatide (2.7%) in that trial.
- "Which is better" has no answer without naming what you are optimising for. Weight, cardiovascular evidence, tolerability, cost and supply point in different directions.
What is actually different about them
Semaglutide acts on one receptor. Tirzepatide acts on two. Semaglutide is a GLP-1 receptor agonist. Tirzepatide is a dual agonist at both GIP and GLP-1 receptors, which is why it is sometimes described as a different class rather than a stronger version of the same thing.
| Semaglutide | Tirzepatide | |
|---|---|---|
| Receptors | GLP-1 | GIP and GLP-1 |
| Weight-management brand | Wegovy | Zepbound |
| Type 2 diabetes brand | Ozempic (also Rybelsus, oral) | Mounjaro |
| Maximum weight-management dose | 2.4 mg weekly | 15 mg weekly |
| Approved maintenance doses | 2.4 mg | 5, 10 or 15 mg |
| Half-life | About 1 week | About 5 days |
Do not read the dose numbers as potency. 15 mg of tirzepatide is not "six times" 2.4 mg of semaglutide; they are different molecules on different scales. Comparing the milligrams is the single most common mistake people make when switching.
The head-to-head trial
SURMOUNT-5 is the only large direct comparison, and it is unusually clean. 751 adults with obesity and without type 2 diabetes were randomised to tirzepatide or semaglutide, both titrated to the maximum tolerated dose, for 72 weeks.
| Measure | Tirzepatide | Semaglutide |
|---|---|---|
| Mean body weight reduction | 20.2% | 13.7% |
| Mean weight lost | 22.8 kg | 15.0 kg |
| Waist circumference change | −18.4 cm | −13.0 cm |
| Stopped for gastrointestinal side effects | 2.7% | 5.6% |
Tirzepatide also produced greater improvements in blood pressure, HbA1c, fasting insulin, triglycerides and HDL cholesterol at 72 weeks. On weight and on most cardiometabolic markers, this is not a close result.
Two caveats worth carrying. The trial was open-label, so nobody was blinded. And a group mean is not a prediction: the spread inside each arm is wide, and plenty of individuals on semaglutide lost more than the tirzepatide average.
Where semaglutide still leads
Semaglutide has a completed cardiovascular outcomes trial. Tirzepatide does not yet.
SELECT randomised 17,604 adults with established cardiovascular disease and obesity, without diabetes, and followed them for a mean of 39.8 months. Major adverse cardiovascular events occurred in 6.5% on semaglutide against 8.0% on placebo — a 20% relative reduction, or about 1.5 fewer events per 100 people over three and a half years.
That is a different kind of evidence from a weight number. If you are on one of these medications partly because of cardiovascular risk, the drug with the outcomes trial behind it is not obviously the second choice, whatever the scale says. This is exactly the trade-off worth naming out loud with a prescriber rather than deciding from a percentage.
Tolerability and clearance
In the head-to-head trial, fewer people stopped tirzepatide over gastrointestinal side effects than stopped semaglutide — 2.7% against 5.6%. Both are low numbers. Most people on either drug get through titration.
The clearance difference matters when stopping or switching. Tirzepatide's half-life is about five days, semaglutide's about a week, so tirzepatide is functionally cleared in roughly 25 days against 34. You can run your own dates through the half-life calculator.
Tirzepatide also has three approved maintenance doses where semaglutide has one, which gives a prescriber more room to trade a little efficacy for tolerability without stopping treatment. See Zepbound maintenance.
Choosing between them
The honest version: this is rarely a free choice. Coverage, supply and what your prescriber will write decide it far more often than the trial data does.
| If your priority is | The evidence points to |
|---|---|
| Maximum weight reduction | Tirzepatide, by 6.5 percentage points over 72 weeks |
| Proven cardiovascular event reduction | Semaglutide — it has the completed outcomes trial |
| Fewer discontinuations for gut side effects | Tirzepatide, in the head-to-head |
| Flexibility on maintenance dose | Tirzepatide — three approved maintenance doses to semaglutide's one |
| An oral option | Semaglutide — Rybelsus is a daily tablet |
| Faster washout before surgery or pregnancy | Tirzepatide, by roughly nine days |
Common questions
- Is tirzepatide better than semaglutide?
- For weight reduction, the head-to-head evidence says yes: 20.2% versus 13.7% over 72 weeks in SURMOUNT-5. For proven cardiovascular event reduction, semaglutide currently has evidence tirzepatide does not, from the 17,604-person SELECT trial. "Better" depends entirely on which of those you are optimising for.
- Can I switch from semaglutide to tirzepatide?
- Yes, and many people do, but it is not a milligram-for-milligram conversion — they are different molecules with different dose ladders, and switching usually means re-titrating from the starting dose. It is a prescriber decision.
- Which has fewer side effects?
- The side effect profiles are similar in kind — mostly gastrointestinal, mostly during dose escalation. In SURMOUNT-5, fewer people stopped tirzepatide over them (2.7%) than semaglutide (5.6%).
- Is 15 mg of tirzepatide the same as 2.4 mg of semaglutide?
- No. They are different molecules and the milligram scales are not comparable. Both are the top of their own approved ladder for weight management, which is the only sense in which they correspond.
Sources
Every figure on this page traces to one of these. Regulatory documents and peer-reviewed primary research only — see our editorial policy for what we accept as a source.
- SURMOUNT-5: Greater Loss of Weight, Waist Circumference With Tirzepatide Than Semaglutide. American College of Cardiology journal scan of the NEJM trial, 2025. View source
- Lincoff AM et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine, 2023. View source
- Aronne LJ et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA, 2024. View source
- WEGOVY (semaglutide) injection, US prescribing information. FDA, 2025. View source
- GLP-1 Agonists: What They Are, How They Work & Side Effects. Cleveland Clinic. View source
Compare your own curve, not the average
GLPme plots your weight against the published trial curves for the drug you are actually on, so a slow month reads as a slow month. Core tracking is free.
