No dose conversion existsNeither the Zepbound nor the Mounjaro label gives a conversion from semaglutide. Both start tirzepatide at 2.5 mg.[5][4] The Zepbound label says it should not be used together with any GLP-1 receptor agonist.[5] Switching is a prescriber decision.
The difference in mechanism
The label describes tirzepatide as “a GIP receptor and GLP-1 receptor agonist.”[5] Semaglutide acts on the GLP-1 receptor only. Both were given once weekly by injection in the trials below.[1]
Tirzepatide vs semaglutide for weight loss (SURMOUNT-5)
751 adults with obesity and without type 2 diabetes were randomized to tirzepatide at the maximum tolerated dose (10 or 15 mg) or semaglutide at the maximum tolerated dose (1.7 or 2.4 mg), open-label, for 72 weeks.[1]
- −20.2%tirzepatide, average weight change
- −13.7%semaglutide, average weight change
- −18.4 cmtirzepatide, waist circumference
- −13.0 cmsemaglutide, waist circumference
Lilly states the 20.2% vs 13.7% figures are “based on the treatment-regimen estimand”, which counts everyone randomized.[2]
SURPASS-2: type 2 diabetes
1,879 adults with type 2 diabetes on metformin were randomized to tirzepatide 5, 10 or 15 mg or semaglutide 1 mg for 40 weeks.[3]
| Outcome | Tirzepatide 5 mg | 10 mg | 15 mg | Semaglutide 1 mg |
|---|---|---|---|---|
| HbA1c change, percentage points (paper) | −2.01 | −2.24 | −2.30 | −1.86 |
| Body weight change, kg (Mounjaro label) | −7.6 | −9.3 | −11.2 | −5.7 |
HbA1c figures are from the NEJM paper; weight figures are from the Mounjaro label.[3][4]
What the SURMOUNT-5 averages mean in pounds
Applying the average percentage changes to example starting weights shows the size of the gap. This is arithmetic on group averages, not a prediction for any person.
| Starting weight | Tirzepatide (−20.2%) | Semaglutide (−13.7%) | Difference |
|---|---|---|---|
| 200 lb | -40.4 lb | -27.4 lb | 13.0 lb |
| 230 lb | -46.5 lb | -31.5 lb | 15.0 lb |
| 260 lb | -52.5 lb | -35.6 lb | 16.9 lb |
| 300 lb | -60.6 lb | -41.1 lb | 19.5 lb |
Tirzepatide vs semaglutide side effects
Both drugs mainly cause digestive side effects. In SURMOUNT-5, the most common adverse events in both groups were gastrointestinal, mostly mild to moderate, and occurred primarily during dose escalation.[1] Tirzepatide's own rates by dose are on Zepbound side effects.
Switching between them
There is no conversion chart between semaglutide and tirzepatide in either FDA label, and the Zepbound label starts every patient at 2.5 mg weekly.[5] The brand-level comparison, including switching from Wegovy, is on Zepbound vs Wegovy.
Reading these results fairly
Both trials favored tirzepatide, but their design limits what they show.
- SURMOUNT-5 was open-label: participants knew which drug they had.[1]
- The semaglutide dose in SURPASS-2 (1 mg) was lower than the 1.7–2.4 mg doses used in SURMOUNT-5.[3][1]
- Both trials were funded by Eli Lilly, the maker of tirzepatide.[1][3]
- Each trial studied one population; results in other groups may differ.
- Averages say nothing about which drug suits a particular person.
Related
- Tirzepatide resultsSURMOUNT-1 by dose
- Zepbound vs MounjaroTwo labels for one drug
- Side effectsLabel tables by dose
Frequently asked questions
Which causes more weight loss, tirzepatide or semaglutide?
In the only head-to-head obesity trial, SURMOUNT-5, average weight change was −20.2% with tirzepatide and −13.7% with semaglutide after 72 weeks.[1]
What is the semaglutide equivalent of tirzepatide 5 mg?
Which is better, tirzepatide or semaglutide?
For average weight loss, tirzepatide did better in the one head-to-head obesity trial (−20.2% vs −13.7%). Which suits a person depends on more than averages and is a prescriber's call.[1]
Which is safer, tirzepatide or semaglutide?
SURMOUNT-5 found gastrointestinal events were the most common side effects with both, mostly mild to moderate. It did not establish that either is safer.[1]
Can I take tirzepatide and semaglutide together?
The Zepbound label says using it with any GLP-1 receptor agonist is not recommended.[5]
Sources
- Aronne LJ et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5)
- Lilly's Zepbound superior to Wegovy in head-to-head trial (SURMOUNT-5 topline, estimand)
- Frías JP et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2)
- Mounjaro (tirzepatide) injection: prescribing information and Instructions for Use
- Zepbound (tirzepatide) injection: prescribing information, Medication Guide and Instructions for Use
- Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)