Semaglutide vs Tirzepatide
The two approved GLP-1 drugs went head to head. What does the result mean for you?
Reviewed by the amino101 editorial team. , first published .
Semaglutide and tirzepatide are the two approved weekly injectables for weight management, and they are the comparison most people actually face. Semaglutide, sold as Ozempic and Wegovy, activates the GLP-1 receptor and produced about 15 percent weight loss over 68 weeks in STEP 1. Tirzepatide, sold as Mounjaro and Zepbound, activates GLP-1 and GIP receptors and produced about 20.9 percent at the 15 mg dose over 72 weeks in SURMOUNT-1. The direct comparison came in SURMOUNT-5, where tirzepatide produced greater weight loss than semaglutide 2.4 mg, roughly 20 versus 14 percent at 72 weeks, in adults with obesity and no diabetes. That is one trial, and individual response varies more than the averages suggest, but it settled the question of which is stronger on average. Semaglutide keeps advantages of its own: the longest track record, the SELECT cardiovascular outcomes trial, lower cost per mg, and an oral form. This page compares dosage, side effects and evidence for educational purposes only.
| Semaglutide | Tirzepatide | |
|---|---|---|
| Typical dosage | 0.25 mg (starting dose) | 2.5 mg (starting dose) |
| Frequency | once weekly | once weekly |
| Route | Subcutaneous, Oral | Subcutaneous |
| Half-life | About 7 days (roughly 165 hours) | About 5 days (roughly 117 hours) |
| Cycle | ongoing, step up every 4 weeks through 0.5, 1.0, 1.7 and 2.4 mg | ongoing, increase by 2.5 mg every 4 weeks as tolerated |
| Research level | Extensively studied | Extensively studied |
| Human trials | Approved drug | Approved drug |
| Status | FDA approved as Ozempic, Wegovy and Rybelsus. Compounded and grey-market vials are not approved products. | FDA approved as Mounjaro and Zepbound. Grey-market vials are not the approved product. |
| Effects timeline | appetite drops within 1 to 2 weeks, steady weight loss from about week 4 once past 0.5 mg, plateau around 12 to 18 months | appetite drops within the first 1 to 2 weeks, weight loss builds from about week 4, plateau around 12 to 18 months |
Key differences
Semaglutide vs Tirzepatide dosage
Dosage patterns reported in research and community protocols, by goal. Taken from each compound page. Not a prescription.
| Goal | Dosage | Frequency |
|---|---|---|
| Weeks 1 to 4, tolerance | 0.25 mg | once weekly |
| Weeks 5 to 8 | 0.5 mg | once weekly |
| Weeks 9 to 12 | 1.0 mg | once weekly |
| Weeks 13 to 16 | 1.7 mg | once weekly |
| Week 17 onward, maintenance | 2.4 mg, or the lowest step that works | once weekly |
| Goal | Dosage | Frequency |
|---|---|---|
| Weeks 1 to 4, tolerance | 2.5 mg | once weekly |
| Weeks 5 to 8 | 5 mg | once weekly |
| Weeks 9 to 12 | 7.5 mg | once weekly |
| Weeks 13 to 16 | 10 mg | once weekly |
| Week 17 onward, if still needed | 12.5 to 15 mg | once weekly |
Convert any of these to syringe units in the dosage calculator.
Side effects compared
- ▲Nausea, especially the first few days after each dose increase
- ▲Constipation or diarrhea
- ▲Burping, reflux and early fullness
- ▲Fatigue and low energy from eating less
- ▲Injection site redness or itching
- ▲Nausea and reduced appetite, worst right after each dose increase
- ▲Diarrhea or constipation
- ▲Burping, reflux and indigestion
- ▲Fatigue during the first weeks of each step
- ▲Injection site reactions
Which should you choose?
Semaglutide is the better fit if you want the lowest cost per mg, the longest safety record, or the cardiovascular outcome data from SELECT. It is also the only one of the two with an oral form and the one paired with cagrilintide in the cagrilintide and semaglutide stack. Expect more nausea during titration and plan each step at 4 weeks minimum.
Tirzepatide is the better fit for most people who want maximum weight loss with the fewest stomach complaints. It beat semaglutide in SURMOUNT-5, has a sleep apnea indication, and plenty of people hold at 5 or 7.5 mg rather than pushing to 15. The 2.5 mg tolerance step is not a treatment dose, so judge it after the second or third step.
Tirzepatide is the stronger drug and the gentler one, and for most people starting fresh that settles it. SURMOUNT-5 showed more weight loss in a direct comparison, and the GIP component appears to soften the nausea that drives people off semaglutide. Semaglutide still wins in three situations. If cost is the constraint, it is cheaper per mg and more widely compounded. If you have existing cardiovascular disease, SELECT gave semaglutide a 20 percent reduction in major cardiac events and tirzepatide does not yet have an equivalent published outcome trial. And if you are already on semaglutide and losing weight at a tolerable dose, there is no reason to switch for a bigger average. One caution on supply: in April 2026 the FDA proposed removing both from the 503B bulks list, with no final decision as of October 2026. Both schedules are at the semaglutide dosage chart and the tirzepatide dosage chart.
Stacking: Not stacked together. Semaglutide is paired with cagrilintide in the CagriSema program, and tirzepatide is sometimes paired with ipamorelin in community protocols, without trial support.
Semaglutide is a once-weekly GLP-1 receptor agonist that cuts appetite and slows digestion, producing average weight loss around 15 percent in trials. It is the molecule behind the Ozempic and Wegovy brand names.
Tirzepatide is a once-weekly peptide that activates both the GIP and GLP-1 receptors, producing average weight loss of about 20 percent at the top dose in trials. It is sold as Mounjaro for diabetes and Zepbound for weight management and sleep apnea.
Semaglutide vs Tirzepatide: frequently asked
Is tirzepatide better than semaglutide for weight loss?
On average, yes. In SURMOUNT-5, tirzepatide produced greater weight loss than semaglutide 2.4 mg in a direct comparison, about 20 versus 14 percent at 72 weeks. That is one trial in people without diabetes, and some individuals respond better to semaglutide, so the average is a guide rather than a guarantee.
Which has fewer side effects, semaglutide or tirzepatide?
Tirzepatide is generally reported as gentler on the stomach at equivalent weight loss, which is attributed to the GIP component. The side effect list is the same for both: nausea, constipation, diarrhea, reflux, fatigue, and hair shedding during rapid loss. The MHRA issued an alert in January 2026 about acute pancreatitis as an infrequent but potentially fatal side effect of the whole class.
Can you take semaglutide and tirzepatide together?
No. They act on overlapping receptors and there is no trial of the combination. Running both would stack GI effects without a known benefit. If you want a second mechanism on top of a GLP-1 drug, cagrilintide is the one with trial data alongside semaglutide.
How do you convert semaglutide dose to tirzepatide?
There is no mg to mg conversion; the two molecules are not equivalent. The usual approach when switching is to start tirzepatide at 2.5 or 5 mg regardless of the semaglutide dose and step up from there, since the half-lives overlap for a few weeks. A dosage chart for each is linked above.
Is semaglutide or tirzepatide cheaper?
Semaglutide is cheaper per mg in branded, compounded and grey market forms. Tirzepatide costs more, but Lilly sells single dose Zepbound vials direct in the US, which narrows the gap for some people. Compounded supply of both may change if the FDA finalizes its 2026 proposal to remove them from the 503B bulks list.
Does microdosing semaglutide or tirzepatide work?
No controlled trial supports microdosing for weight loss. Common descriptions are semaglutide 0.05 to 0.5 mg weekly or tirzepatide 0.5 to 2.5 mg weekly. The SURMOUNT-MAINTENANCE trial is testing reduced tirzepatide maintenance doses with results expected late 2026. See GLP-1 microdosing.
Related reading
Weight loss beyond semaglutide alone
Weight loss while limiting muscle loss
Three generations of GLP-1 drugs. What actually separates them?
The triple agonist beats the dual agonist on paper. Is it worth waiting for, or buying early?
First generation versus third. How big is the gap, and what do you give up to close it?
Dosage
Sources
- Once-weekly semaglutide in adults with overweight or obesity (STEP 1). New England Journal of Medicine, 2021
- Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). New England Journal of Medicine, 2022
- Tirzepatide versus semaglutide for weight loss in adults with obesity without diabetes (SURMOUNT-5). New England Journal of Medicine, 2025
- Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). New England Journal of Medicine, 2023