Semaglutide vs tirzepatide: in the only large head-to-head trial, SURMOUNT-5, tirzepatide produced more weight loss (20.2% vs 13.7% at 72 weeks). Both are FDA-approved, once-weekly prescription drugs with similar gastrointestinal side effects. Semaglutide is sold as Ozempic and Wegovy, and tirzepatide as Mounjaro and Zepbound. Which one suits a person depends on their health, other conditions and insurance, so it's a decision to make with a clinician.
Medical disclaimer: This page summarizes published trials and FDA information for general education. It isn't medical advice and contains no dosing guidance. These are prescription drugs. Talk to a licensed clinician before starting, stopping or switching any medication. Last reviewed September 26, 2026.
The approved products
| Semaglutide | Tirzepatide | |
|---|---|---|
| Type 2 diabetes brand | Ozempic, approved December 5, 2017 | Mounjaro, approved May 13, 2022 |
| Weight management brand | Wegovy, approved June 4, 2021 | Zepbound, approved November 8, 2023 |
| Other approved uses (selected) | Wegovy: cardiovascular risk reduction (March 2024) and MASH (August 2025) (history) | Zepbound: moderate to severe obstructive sleep apnea in adults with obesity (FDA, December 20, 2024) |
| Form | Weekly injection; Wegovy pill approved December 22, 2025 (history) | Weekly injection |
According to Drugs.com's approval history, FDA also approved Mounjaro to reduce the risk of major cardiovascular events on August 28, 2026.
How they work
Both drugs mimic gut hormones that are released after eating.
- Semaglutide "mimics a hormone called glucagon-like peptide-1 (GLP-1) that targets areas of the brain that regulate appetite and food intake," according to FDA's Wegovy announcement.
- Tirzepatide "activates receptors of hormones secreted from the intestine (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) to reduce appetite and food intake," per FDA's Zepbound announcement.
Tirzepatide acts on one more receptor (GIP). The trials don't prove that the extra receptor causes the difference in weight loss, but it's the main pharmacological distinction.
Head-to-head: SURMOUNT-5
SURMOUNT-5 is the direct comparison most people are looking for. It was published in the New England Journal of Medicine in 2025 (Aronne et al., NEJM 2025;393:26-36).
Design (ACC summary; Applied Clinical Trials):
- 751 adults with obesity, or overweight with a weight-related condition, and without type 2 diabetes
- 32 sites in the US and Puerto Rico
- Open-label (participants knew which drug they got), 72 weeks
- Each group took the maximum dose it tolerated
- Sponsored by Eli Lilly, which makes tirzepatide
Results:
| Outcome at 72 weeks | Tirzepatide | Semaglutide |
|---|---|---|
| Average body weight change | -20.2% (about 22.8 kg) | -13.7% (about 15.0 kg) |
| Average waist change | -18.4 cm | -13.0 cm |
| Stopped due to GI side effects | 2.7% | 5.6% |
The difference in weight loss was statistically significant (P<0.001). Tirzepatide users were also more likely to reach 10%, 15%, 20% and 25% weight loss. The ACC summary notes weight loss was about 6% lower in men than women.
Limitations to keep in mind: it's a single trial, it was open-label, it was funded by one of the two manufacturers, and it didn't include people with diabetes. Averages also hide wide individual variation.
The placebo-controlled trials behind each approval
Each drug was also tested against placebo in its own trial program. These trials weren't designed to compare the two drugs, so their numbers shouldn't be set side by side as if they were.
- STEP 1 (semaglutide): 1,961 adults, 68 weeks. Average weight change was -14.9% on semaglutide vs -2.4% on placebo. 4.5% on semaglutide stopped because of gastrointestinal events, vs 0.8% on placebo (ACC; NEJM).
- SURMOUNT-1 (tirzepatide): 2,539 adults, 72 weeks. Average weight loss was 16.0%, 21.4% and 22.5% across three dose groups vs 2.4% on placebo (efficacy estimand, per Lilly; NEJM).
Side effects compared
The two drugs have similar side-effect profiles, dominated by gastrointestinal effects that are most common while the dose is being increased.
Semaglutide (Wegovy). FDA lists nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, indigestion, dizziness, belching, gas and low blood sugar in people with diabetes among the most common side effects (FDA). In STEP 1, serious adverse events occurred in 9.8% on semaglutide vs 6.4% on placebo (ACC).
Tirzepatide (Zepbound). FDA lists nausea, diarrhea, vomiting, constipation, abdominal discomfort, injection site reactions, fatigue, allergic reactions, burping, hair loss and acid reflux (FDA). In SURMOUNT-1, Lilly reported these rates across the three dose groups vs placebo (Lilly):
- Nausea: 24.6% to 33.3% vs 9.5%
- Diarrhea: 18.7% to 23.0% vs 7.3%
- Vomiting: 8.3% to 12.2% vs 1.7%
- Constipation: 11.7% to 17.1% vs 5.8%
- Stopped due to adverse events: 4.3% to 7.1% vs 2.6%
Shared warnings. Both carry a boxed warning because they caused thyroid C-cell tumors in rodents. It's unknown whether they cause these tumors, including medullary thyroid cancer, in humans. FDA's Wegovy announcement also notes a contraindication for people with medullary thyroid carcinoma or MEN 2 (FDA on Wegovy; FDA on Zepbound). FDA also lists warnings for pancreatitis, gallbladder problems, low blood sugar, kidney injury, diabetic eye complications and suicidal thoughts or behavior for Zepbound (FDA). The full prescribing information is the authoritative list.
Cost and coverage basics
Prices change often, so treat any figure as a snapshot:
- Self-pay programs. Both manufacturers sell directly to patients with a prescription. As of a March 2026 summary, LillyDirect listed Zepbound from $299 a month for the starting dose, and NovoCare listed most injectable Wegovy and Ozempic doses at $349 a month (Affinity Whole Health). Check the manufacturer's site for current prices.
- Insurance. Coverage depends on your plan and on the indication. A plan may cover a drug for type 2 diabetes, sleep apnea or cardiovascular risk but not for weight loss alone. Ask your insurer which brand, if any, is on its formulary and whether prior authorization is required.
- Compounded versions. FDA ended its shortage-related flexibility for compounded tirzepatide and semaglutide in 2025, after both shortages were resolved (FDA).
A note on unapproved versions
Semaglutide and tirzepatide are also sold online as "research" chemicals. FDA says it has warned companies that "illegally sold unapproved drugs containing semaglutide, tirzepatide, retatrutide, survodutide or mazdutide that are falsely labeled 'for research purposes' or 'not for human consumption'" (FDA). Those products aren't the approved drugs, weren't tested in these trials and aren't regulated for quality. We list them for research use only, with no dosing content. See are peptides legal? and, for the investigational triple agonist, retatrutide side effects.
Bottom line
In SURMOUNT-5, tirzepatide produced more average weight loss than semaglutide, and fewer people stopped it because of gastrointestinal side effects. Both are approved drugs with similar side effects and the same thyroid boxed warning. Semaglutide has a pill form and a cardiovascular indication for Wegovy, and tirzepatide has a sleep apnea indication for Zepbound. The right choice for any one person is a conversation with a clinician, not a trial average.
Sources are linked inline. Prices and approvals change often; we'll update this page as they do.
Research-grade vendor prices and COAs: tirzepatide vendors and semaglutide vendors.