Semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound) are the two medicines people compare most often. They are both weekly injectable peptides that copy gut hormones, but they are not the same. This side-by-side guide covers how they differ, what the research shows, and what to ask your prescriber.
Key takeaways
- Semaglutide acts on one receptor (GLP-1). Tirzepatide acts on two (GIP and GLP-1).
- Both are FDA-approved, but for different lists of uses under different brand names.
- In the SURMOUNT-5 head-to-head trial, tirzepatide led to more average weight loss (20.2% vs. 13.7% over 72 weeks).
- Side effects and boxed warnings are very similar.
- Their doses are on different scales. Milligrams of one do not equal milligrams of the other.
At a glance
| Semaglutide | Tirzepatide | |
|---|---|---|
| Brand names | Ozempic, Wegovy, Rybelsus | Mounjaro, Zepbound |
| Receptors | GLP-1 | GIP and GLP-1 |
| How often (injection) | Once weekly | Once weekly |
| Pill version | Yes (Rybelsus, Wegovy pill) | No |
| Half-life | About 1 week | About 5 days |
| Type 2 diabetes | Ozempic, Rybelsus | Mounjaro |
| Weight management | Wegovy (injection and pill) | Zepbound |
| Heart risk reduction | Ozempic, Rybelsus and Wegovy, in specific groups | Mounjaro, in certain adults with type 2 diabetes |
| Other approved uses | Kidney risk in type 2 diabetes with CKD (Ozempic); MASH liver disease (Wegovy) | Obstructive sleep apnea with obesity (Zepbound) |
| Missed weekly dose (per label) | Ozempic: within 5 days | Zepbound: within 4 days (96 hours) |
| Boxed warning | Thyroid C-cell tumors in rodents | Thyroid C-cell tumors in rats |
Approved uses change as new trials finish, so check current labels with your pharmacist. For more depth, see semaglutide explained and tirzepatide explained.
How they work differently
Both drugs copy GLP-1, a hormone your gut releases after meals. GLP-1 helps release insulin when blood sugar is high, lowers glucagon, slows stomach emptying and signals fullness to the brain.
Tirzepatide also activates the GIP receptor. GIP is a second gut hormone that helps release insulin and is involved in how the body handles energy and fat. Researchers think acting on both pathways may explain some of tirzepatide's added effect, though the full picture is still being studied.
What the head-to-head trial found
SURMOUNT-5 was a phase 3b trial published in the New England Journal of Medicine in 2025. It compared the two drugs directly in 751 adults with obesity who did not have diabetes. People took the highest dose they could tolerate of either drug (tirzepatide 10 or 15 mg, or semaglutide 1.7 or 2.4 mg, once weekly) for 72 weeks. These were trial doses, not recommendations.
Results, as averages:
| Result at 72 weeks | Tirzepatide | Semaglutide |
|---|---|---|
| Average body weight change | -20.2% | -13.7% |
| Average weight lost | 22.8 kg (about 50 lb) | 15.0 kg (about 33 lb) |
| Average waist change | -18.4 cm (about 7.2 in) | -13.0 cm (about 5.1 in) |
| Stopped due to stomach side effects | 2.7% | 5.6% |
Some context helps here:
- These are averages. Some people lost much more and some much less on each drug.
- The trial did not include people with type 2 diabetes, so results may differ for them.
- Weight loss was about 6 percentage points lower for men than women in both groups.
- A higher-dose Wegovy (7.2 mg) was approved in 2026 for some adults. SURMOUNT-5 did not test that dose.
Side effects compared
Both medicines share the same main side effects: nausea, diarrhea, vomiting, constipation, stomach pain and lower appetite. These usually show up when starting or raising a dose and often ease over time.
Both labels also warn about pancreatitis, gallbladder problems, kidney problems from dehydration, low blood sugar when used with certain diabetes medicines, and allergic reactions. Both carry a boxed warning about thyroid C-cell tumors seen in rodents and should not be used by people with a personal or family history of medullary thyroid carcinoma or MEN 2.
One difference to know: the Zepbound label warns that tirzepatide can make oral birth control pills less effective, especially after starting and after dose increases. Ask your prescriber about backup birth control.
Doses are not interchangeable
Semaglutide and tirzepatide use different dose scales. A "2.5 mg" dose means something very different for each drug, so you cannot swap one for the other milligram for milligram. If you switch, your prescriber will choose a new starting point and plan. PepSteady does not recommend doses.
Practical differences
- Pill option: Semaglutide comes as daily tablets (Rybelsus for diabetes, Wegovy pill for weight). Tirzepatide is injection only.
- Devices: Each brand has its own pens, and Zepbound is also available in vials and a multi-dose KwikPen.
- Coverage and cost: Insurance rules vary widely by plan and by diagnosis. Your pharmacist or plan can tell you what is covered.
- Supply and compounding: FDA declared both shortages over (tirzepatide in late 2024, semaglutide in February 2025). In April 2026 FDA proposed excluding both from the outsourcing-facility bulks list. Compounded versions are not FDA-approved.
Questions to ask your prescriber
- Which of my health conditions does each drug have an approval for?
- Which does my insurance cover, and is there a cheaper option?
- How will we handle stomach side effects if they happen?
- Do any of my current medicines, including birth control, need changes?
- How will we measure progress besides the scale?
If you are looking for a licensed provider, our telehealth guide explains what to look for.
The bottom line
Semaglutide and tirzepatide are both effective weekly medicines, with tirzepatide adding a second hormone pathway and showing more average weight loss in a head-to-head trial. Side effects are similar, approved uses differ, and doses are not interchangeable. The right choice depends on your health, coverage and tolerance, and it is a decision to make with your prescriber.
Sources
- ACC: SURMOUNT-5 trial summary (tirzepatide vs. semaglutide)
- DailyMed: Ozempic (semaglutide) prescribing information
- DailyMed: Zepbound (tirzepatide) prescribing information
- FDA: Proposal to exclude semaglutide, tirzepatide and liraglutide from the 503B bulks list
- Novo Nordisk: Wegovy pill approved in the US
Frequently asked questions
Which works better for weight loss, semaglutide or tirzepatide?
In the SURMOUNT-5 head-to-head trial, adults with obesity lost an average of 20.2% of body weight on tirzepatide versus 13.7% on semaglutide over 72 weeks. Averages do not predict any one person's result, and the best choice depends on your health, coverage and how you tolerate the medicine.
Do they have the same side effects?
They share the same main side effects, mostly nausea, diarrhea, vomiting and constipation, and both carry the same type of boxed warning about thyroid C-cell tumors in rodents. In SURMOUNT-5, stopping because of stomach side effects was somewhat more common with semaglutide.
Can I switch from one to the other?
Switching is possible, but only your prescriber should plan it. The two drugs use different dose scales, so a dose of one does not equal the same number of milligrams of the other.