Semaglutide vs tirzepatide
These are the two approved weight-loss drugs most people are choosing between. They have been tested against each other directly, and tirzepatide produced more weight loss. That is not the whole decision.
- More weight loss on average: tirzepatide
- Available as a pill: semaglutide only
- Proven to cut heart attacks and strokes in people with heart disease: semaglutide
- Lowest starting price: semaglutide pill, $149 a month
The head-to-head trial
SURMOUNT-5 put the two drugs in the same trial: 751 adults with obesity and without type 2 diabetes, each drug taken up to its maximum tolerated dose for 72 weeks. Results were published in the New England Journal of Medicine in May 2025.
| Result at 72 weeks | Tirzepatide | Semaglutide |
|---|---|---|
| Average weight loss | 20.2% | 13.7% |
| Lost at least 10% | 81.6% | 60.5% |
| Lost at least 15% | 64.6% | 40.1% |
| Lost at least 25% | 31.6% | 16.1% |
| Waist reduction | 18.4 cm | 13.0 cm |
Three things to know before leaning on those numbers:
- Eli Lilly, which makes tirzepatide, paid for the trial. The figures match what each drug achieved in its own earlier blinded trials, which is reassuring.
- It was not blinded. Participants knew which drug they were on.
- Semaglutide topped out at 2.4 mg. The Wegovy label has since added a 7.2 mg weekly dose, which this trial did not test.
Side effects in both groups were mostly in the gut. The tirzepatide group had more injection-site reactions.
Where they differ beyond the scale
| Semaglutide | Tirzepatide | |
|---|---|---|
| Brands | Wegovy, Ozempic, Rybelsus | Zepbound, Mounjaro |
| How it works | Acts on one receptor, GLP-1 | Acts on two, GIP and GLP-1 |
| Forms | Weekly injection or daily pill | Weekly injection only |
| Heart outcomes | The SELECT trial showed fewer major cardiovascular events in people with established heart disease | No equivalent result in people without diabetes yet |
| Other approved uses | Licensed for adolescents | Approved for obstructive sleep apnea |
| Top label dose | 7.2 mg injection, 25 mg pill | 15 mg |
| Evidence grade | A | A |
What each costs without insurance
| Semaglutide (NovoCare) | Tirzepatide (LillyDirect) | |
|---|---|---|
| Starting dose | $149 pill, or $199 pen for the first two fills | $299 |
| Maintenance | $299 pill, $349 pen | $449 with on-time refills, up to $699 without |
Prices were checked in late October and early November 2026. The details, including the 45-day refill rule on Zepbound, are on the costs page.
How people actually choose
- If you want the most weight loss and can inject: the head-to-head data favors tirzepatide.
- If you will not inject: semaglutide is the only one with a pill.
- If you have heart disease: semaglutide has the outcome trial. Raise this with your prescriber.
- If you have sleep apnea: tirzepatide carries that approval.
- If cost decides: the Wegovy pill is the cheapest brand-name route at every stage.
- If insurance covers one and not the other: that usually settles it. A covered drug at a $25 copay beats a better drug at $449.
Both carry the same boxed warning about thyroid C-cell tumors, and with both, weight tends to return when treatment stops. A 13.7% average loss is still a large result; the weaker drug in this comparison is not a weak drug.
Sources
- Eli Lilly: SURMOUNT-5 detailed results, May 2025
- Patient Care: SURMOUNT-5 results, citing Aronne et al., NEJM 2025
- Weill Cornell release: trial size, design and funding
- Diabetes on the Net: open-label design, SELECT and other approved uses
- American Pharmacists Association: injection-site reactions and limitations
- GLP Chart: Wegovy cash prices and Zepbound cash prices, November 2026