Semaglutide vs Tirzepatide
What the head-to-head trial found, and how the two compounds differ.
In the one trial that put them side by side (SURMOUNT-5, 751 adults with obesity and no diabetes, 72 weeks), tirzepatide averaged 20.2% weight loss and semaglutide 13.7%. Everything below comes from the published trials.
Side by side
| Semaglutide | Tirzepatide | |
|---|---|---|
| Receptors | GLP-1 | GIP + GLP-1 |
| Dosing | Once weekly injection | Once weekly injection |
| Top doses in SURMOUNT-5 | 1.7 mg or 2.4 mg | 10 mg or 15 mg |
| Weight loss at 72 weeks (SURMOUNT-5) | 13.7% | 20.2% |
| Lost 25% or more (SURMOUNT-5) | 16.1% | 31.6% |
| Waist change (SURMOUNT-5) | −13.0 cm | −18.4 cm |
| Own placebo trial | 14.9% at 68 weeks, 2.4 mg (STEP-1) | 20.9% at 72 weeks, 15 mg (SURMOUNT-1) |
| Brand names | Ozempic, Wegovy | Mounjaro, Zepbound |
What is the difference between semaglutide and tirzepatide?
Semaglutide acts on one receptor, GLP-1. Tirzepatide acts on two, GIP and GLP-1. Both are once-weekly injections that slow stomach emptying and reduce appetite. In the head-to-head SURMOUNT-5 trial, tirzepatide produced more weight loss: 20.2% versus 13.7% at 72 weeks.
Which one causes more weight loss?
Tirzepatide. In SURMOUNT-5, adults on the highest dose they tolerated of each drug lost an average of 20.2% on tirzepatide (10 or 15 mg) and 13.7% on semaglutide (1.7 or 2.4 mg) after 72 weeks. 31.6% of the tirzepatide group lost at least a quarter of their body weight, against 16.1% on semaglutide.
What was SURMOUNT-5?
A phase 3b, open-label trial run by Eli Lilly and published in the New England Journal of Medicine in 2025. 751 adults with obesity but without type 2 diabetes were randomly assigned 1:1 to either drug for 72 weeks. Weight loss and waist size were the main measures. Because it was open-label, participants knew which drug they were on.
How do their own placebo trials compare?
Semaglutide 2.4 mg produced 14.9% weight loss at 68 weeks in STEP-1. Tirzepatide 15 mg produced 20.9% at 72 weeks in SURMOUNT-1. These were separate trials with different people, so SURMOUNT-5 is the fairer comparison.
What are the side effects?
For both, the most common side effects are gastrointestinal: nausea, diarrhea, vomiting and constipation. In SURMOUNT-5 most were mild to moderate and happened mainly while the dose was being increased. Both drug labels carry warnings for pancreatitis, gallbladder disease and thyroid C-cell tumors seen in rodents.
How are they dosed?
Both are injected once a week and started low, then raised in steps to limit stomach side effects. In SURMOUNT-5 each group was raised to the highest dose they tolerated: 10 or 15 mg of tirzepatide, 1.7 or 2.4 mg of semaglutide.
Where does retatrutide fit?
Retatrutide adds a third receptor, glucagon, on top of GIP and GLP-1. It is still investigational. In its phase 3 TRIUMPH-1 trial the 12 mg dose produced 28.3% weight loss at 80 weeks. It has not been tested head to head against either drug.
The trials
- SURMOUNT-5: Aronne et al., NEJM 2025 (PMID 40353578)
- STEP-1: Wilding et al., NEJM 2021 (PMID 33567185)
- SURMOUNT-1: Jastreboff et al., NEJM 2022 (PMID 35658024)
Keep reading
- Side-by-side compound profiles — Half-life, dose range and current vendor prices for both.
- Tirzepatide prices — Current listings and price per mg.
- Semaglutide prices — Current listings and price per mg.
- Retatrutide FAQ — The triple-receptor compound and its TRIUMPH trial numbers.