Comparisons
Tirzepatide vs semaglutide: head-to-head results and label differences
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Short answer
In the only head-to-head obesity trial, SURMOUNT-5, tirzepatide (Zepbound) lowered weight by −20.2% vs −13.7% for semaglutide (Wegovy) at 72 weeks, a 6.5-point gap at maximum tolerated doses. Tirzepatide acts on GIP and GLP-1 receptors; semaglutide on GLP-1 only. Both are FDA approved as of Oct 19, 2026. It was open-label; the abstract does not name the estimand.
On this page11 sections
| Item | Value | Source |
|---|---|---|
| Tirzepatide receptor targets | GIP and GLP-1 receptors | Eli Lilly, May 13, 2022 |
| Semaglutide receptor target | GLP-1 receptor | Novo Nordisk, Jun 18, 2026 |
| SURMOUNT-5 weight change, week 72 | Tirzepatide −20.2% vs semaglutide −13.7% (least-squares mean; estimand not named) | N Engl J Med, Jul 3, 2025 |
| SURMOUNT-5 design | Open-label phase 3b; 751 adults with obesity, no diabetes; tirzepatide 10/15 mg vs semaglutide 1.7/2.4 mg | N Engl J Med, Jul 3, 2025 |
| SURMOUNT-5 waist change, week 72 | −18.4 cm vs −13.0 cm | N Engl J Med, Jul 3, 2025 |
| SURPASS-2 HbA1c change, week 40 | Tirzepatide 5/10/15 mg −2.01/−2.24/−2.30 points vs semaglutide 1 mg −1.86 | N Engl J Med, Aug 5, 2021 |
| Tirzepatide half-life | About 5 days (Zepbound label section 12.3: 5–6 days) | DailyMed, Aug 28, 2026 |
| Semaglutide half-life | Approximately 1 week | Novo Nordisk, Jun 18, 2026 |
| Zepbound label ladder | 2.5 mg × 4 weeks, then 5 mg; +2.5 mg after ≥4 weeks; maintenance 5, 10 or 15 mg | DailyMed, Aug 28, 2026 |
| Wegovy label ladder | 0.25 → 0.5 → 1 → 1.7 → 2.4 mg every 4 weeks; optional 7.2 mg (Wegovy HD) for adults | Novo Nordisk, Jun 18, 2026 |
| Nausea, top weight dose vs placebo | Zepbound 15 mg 28% vs 8%; Wegovy 2.4 mg 44% vs 16% (separate label tables) | DailyMed, Aug 28, 2026 |
Also useful: Tirzepatide level plotter, Semaglutide level plotter, GLP-1 level plotter (all compounds).
Tirzepatide and semaglutide are the two best-known weekly drugs for weight and type 2 diabetes. Tirzepatide is Eli Lilly’s molecule, sold as Zepbound for weight and Mounjaro for diabetes. Semaglutide is Novo Nordisk’s, sold as Wegovy for weight and Ozempic for diabetes. Unlike most comparisons on this site, these two have been tested against each other directly. Every number below comes from the FDA labels or the trial abstracts. For each drug’s full profile, see the tirzepatide hub and the semaglutide hub.
Side-by-side comparison table
| Item | Tirzepatide | Semaglutide |
|---|---|---|
| Receptor targets | GIP and GLP-1 | GLP-1 |
| Weight-management brand | Zepbound (approved Nov 8, 2023) | Wegovy (approved Jun 4, 2021) |
| Type 2 diabetes brand | Mounjaro (approved May 13, 2022) | Ozempic (approved Dec 5, 2017) |
| Half-life | About 5 days (Zepbound label: 5–6 days) | Approximately 1 week |
| Time to peak | Median 24 hours (range 8–72) | 1–3 days |
| Bioavailability, under the skin | 80% | 89% |
| Weight ladder start | 2.5 mg weekly for 4 weeks | 0.25 mg weekly for 4 weeks |
| Weight maintenance doses | 5, 10 or 15 mg | 1.7 or 2.4 mg (2.4 mg recommended); optional 7.2 mg |
| Missed dose window | Within 4 days (96 hours), else skip | Wegovy: give if next dose is more than 2 days away, else skip |
| Head-to-head weight change (SURMOUNT-5, 72 wk) | −20.2% | −13.7% |
Sources: Zepbound label (DailyMed, Aug 28, 2026), Wegovy label (Novo Nordisk, Jun 18, 2026), Mounjaro approval (Eli Lilly, May 13, 2022), Zepbound approval (FDA, Nov 8, 2023), Drugs@FDA for Ozempic (FDA, Oct 19, 2026) and Wegovy (FDA, Oct 19, 2026), SURMOUNT-5 (N Engl J Med, Jul 3, 2025).
SURMOUNT-5: the head-to-head obesity trial
SURMOUNT-5 randomized 751 adults with obesity and without type 2 diabetes to tirzepatide or semaglutide for 72 weeks (N Engl J Med, Jul 3, 2025). Each person was taken to the maximum tolerated dose: 10 or 15 mg of tirzepatide, or 1.7 or 2.4 mg of semaglutide. It was published online in May 2025 and in print on July 3, 2025.
| Outcome | Tirzepatide 10/15 mg | Semaglutide 1.7/2.4 mg |
|---|---|---|
| Body weight change | −20.2% (95% CI −21.4 to −19.1) | −13.7% (95% CI −14.9 to −12.6) |
| Waist circumference change | −18.4 cm | −13.0 cm |
| Difference in weight change | 6.5 percentage points in favor of tirzepatide | — |
The 6.5-point difference is our subtraction of the two published means; the abstract reports P less than 0.001 for the comparison (New England Journal of Medicine, Jul 3, 2025).
Read these results with three limits in mind:
- Open-label. Participants and investigators knew which drug was given. That can affect behavior, dropout and how side effects are reported.
- Sponsor. Lilly, which makes tirzepatide, funded the trial.
- Estimand not named. The abstract does not say whether −20.2% and −13.7% use a treatment-regimen or an efficacy-style estimand, and we did not verify it in the full text. We report them as least-squares means without a label.
SURMOUNT-5 is still the cleanest comparison available, because both drugs were tested in the same people over the same period.
SURPASS-2: the head-to-head diabetes trial
SURPASS-2 compared three tirzepatide doses with semaglutide 1 mg in 1,879 adults with type 2 diabetes taking metformin. It was open-label and ran 40 weeks (N Engl J Med, Aug 5, 2021).
| Outcome | Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Semaglutide 1 mg |
|---|---|---|---|---|
| HbA1c change (percentage points) | −2.01 | −2.24 | −2.30 | −1.86 |
| Weight change, Mounjaro label (kg) | −7.6 | −9.3 | −11.2 | −5.7 |
| Weight difference vs semaglutide (kg) | −1.9 | −3.6 | −5.5 | — |
Sources: abstract (N Engl J Med, Aug 5, 2021); label weight table (modified intent-to-treat, multiple imputation with retrieved dropout) (DailyMed, Aug 27, 2026).
Ozempic’s label now allows 2 mg as a maximum dose (Novo Nordisk, Jun 1, 2026), which SURPASS-2 did not test. Mounjaro is not indicated for weight loss, even though it lowered weight in this trial.
Label differences
The two molecules are approved for different uses under different brand names. This matters for insurance and for which ladder a prescriber follows.
| Brand | Molecule | Labeled uses |
|---|---|---|
| Zepbound | Tirzepatide | Chronic weight reduction in adults with obesity, or overweight with a weight-related condition; moderate to severe obstructive sleep apnea in adults with obesity |
| Mounjaro | Tirzepatide | Glycemic control in adults and children 10 and older with type 2 diabetes; lowering major cardiovascular event risk in adults with type 2 diabetes at high cardiovascular risk |
| Wegovy | Semaglutide | Weight reduction in adults and children 12 and older; lowering cardiovascular risk in adults with heart disease and obesity or overweight; noncirrhotic MASH with moderate to advanced fibrosis |
| Ozempic | Semaglutide | Adults with type 2 diabetes, including a labeled 1 mg maintenance dose for type 2 diabetes with chronic kidney disease (see the label for the full list) |
Sources: (DailyMed, Aug 28, 2026) (DailyMed, Aug 27, 2026) (Novo Nordisk, Jun 18, 2026) (Novo Nordisk, Jun 1, 2026)
Semaglutide’s cardiovascular claim for Wegovy rests on SELECT, a trial of 17,604 people with heart disease and a BMI of 27 or more without diabetes. Major cardiovascular events occurred in 6.5% on semaglutide vs 8.0% on placebo, a hazard ratio of 0.80 (New England Journal of Medicine, Dec 14, 2023). FDA approved that indication on Mar 8, 2024 (FDA, Mar 8, 2024). Zepbound’s second indication, sleep apnea, was approved on Dec 20, 2024 (FDA, Dec 20, 2024).
The Wegovy label also added a higher dose. Wegovy HD 7.2 mg was approved on Mar 19, 2026 (FDA, Mar 19, 2026) for adults on the weight indication who have tolerated 2.4 mg for at least 4 weeks. In the label’s Study 8, weight change at 72 weeks was −18.8% on 7.2 mg, −15.5% on 2.4 mg and −3.9% on placebo (least-squares mean, intent-to-treat) (Novo Nordisk, Jun 18, 2026). That is a different trial from SURMOUNT-5 and is not a comparison with tirzepatide.
Dose ladders
Both labels raise the dose every 4 weeks, but the steps are very different in size.
- Weekly dose (published steps)
- Modeled amount (mg-eq)
- Stable window
- Weekly dose (published steps)
- Modeled amount (mg-eq)
- Stable window
Zepbound starts at 2.5 mg for 4 weeks, moves to 5 mg, then rises in 2.5 mg increments after at least 4 weeks on the current dose, to a maximum of 15 mg (DailyMed, Aug 28, 2026). Wegovy starts at 0.25 mg and steps every 4 weeks through 0.5, 1 and 1.7 mg to 2.4 mg (Novo Nordisk, Jun 18, 2026). If a dose is not tolerated, the Wegovy label says to consider delaying escalation by 4 weeks. Ask your prescriber before changing a step. To see either ladder laid out with dates, use the tirzepatide titration tool or the semaglutide titration tool.
Half-life and accumulation
Semaglutide stays in the body longer. Its label half-life is about 1 week, and the Wegovy label says it remains in circulation for about 5 to 7 weeks after the last dose (Novo Nordisk, Jun 18, 2026). Tirzepatide’s half-life is about 5 days, and its label gives a time to steady state of 4 weeks (DailyMed, Aug 28, 2026).
| Model value | Tirzepatide | Semaglutide |
|---|---|---|
| Half-life used | 5 days | 7 days |
| Time to peak used | 1 day | 1.5 days |
| Fraction of a dose left after 7 days | 0.3789 | 0.5000 |
| Weekly accumulation ratio | 1.6101 | 2.0000 |
An accumulation ratio of 2.0000 means the steady-state amount is about twice a single dose. Half-life is not a measure of strength: semaglutide accumulates more but produced less weight loss than tirzepatide in SURMOUNT-5. Compare the curves in the tirzepatide plotter and the semaglutide plotter, or both together in the multi-compound plotter.
Side effects from the labels
| Adverse reaction | Zepbound 15 mg | Placebo | Wegovy 2.4 mg | Placebo |
|---|---|---|---|---|
| Nausea | 28% | 8% | 44% | 16% |
| Diarrhea | 23% | 8% | 30% | 16% |
| Vomiting | 13% | 2% | 24% | 6% |
| Constipation | 11% | 5% | 24% | 11% |
| Abdominal pain | 10% | 5% | 20% | 10% |
| Fatigue | 7% | 3% | 11% | 5% |
| Hair loss | 5% | 1% | 3% | 1% |
Sources: (DailyMed, Aug 28, 2026) (Novo Nordisk, Jun 18, 2026)
Do not read this as “semaglutide causes more nausea”. The two tables pool different trials, and the placebo rates differ as well (8% vs 16% for nausea). The Zepbound table pools SURMOUNT-1 and SURMOUNT-2; the Wegovy table pools three STEP trials of up to 68 weeks. Discontinuation for side effects was similar in size: 6.2% on tirzepatide 15 mg vs 2.6% on placebo in SURMOUNT-1 (N Engl J Med, Jul 21, 2022), and 6.8% on Wegovy 2.4 mg vs 3.2% on placebo in the Wegovy weight trials (Novo Nordisk, Jun 18, 2026).
In the diabetes labels, nausea was 18% on Mounjaro 15 mg vs 4% on placebo (DailyMed, Aug 27, 2026) and 20.3% on Ozempic 1 mg vs 6.1% on placebo (Novo Nordisk, Jun 1, 2026). See the tirzepatide side effects guide and the semaglutide side effects guide for full tables.
Cost and savings programs
Lilly and Novo Nordisk both run self-pay and commercial savings programs, and the terms change often. We keep dated prices on dedicated pages: Zepbound savings card, Mounjaro savings card, Wegovy savings card and Ozempic savings card. The tirzepatide cost tool and the semaglutide cost tool estimate a monthly total from those programs.
Compounded versions
Compounded tirzepatide and compounded semaglutide are not FDA approved and are not interchangeable with the brands. FDA states that compounded drugs are not reviewed for safety, effectiveness or quality, and it had received more than 730 adverse-event reports linked to compounded tirzepatide as of May 31, 2026 (FDA, Oct 1, 2026). FDA declared the tirzepatide shortage resolved and reaffirmed that on Dec 19, 2024 (FDA, Dec 19, 2024), and declared the semaglutide injection shortage resolved on Feb 21, 2025 (FDA, Feb 21, 2025). FDA’s April 2026 compounding policy page repeats that compounded drugs are not approved by FDA (FDA, Apr 1, 2026). Talk to your prescriber about approved options.
Frequently asked questions
Tirzepatide vs semaglutide: which is better for weight loss?
- In SURMOUNT-5, the only published head-to-head obesity trial, tirzepatide produced more average weight loss: −20.2% vs −13.7% with semaglutide at 72 weeks in 751 adults with obesity and no diabetes, per the NEJM 2025 abstract. Each drug was given at the maximum tolerated dose. The trial was open-label and Lilly-funded. Averages do not predict any one person's response; talk to your prescriber.
What is the difference between tirzepatide and semaglutide?
- Tirzepatide (Zepbound, Mounjaro) activates both GIP and GLP-1 receptors. Semaglutide (Wegovy, Ozempic) activates GLP-1 receptors only. Their labels also differ: tirzepatide's half-life is about 5 days and semaglutide's about 1 week; Zepbound steps up in 2.5 mg increments to 15 mg, while Wegovy climbs from 0.25 mg to 2.4 mg, with an optional 7.2 mg dose for adults.
Which has more side effects, tirzepatide or semaglutide?
- Both labels list nausea, diarrhea, vomiting and constipation as the most common effects. The Zepbound label reports nausea in 28% on 15 mg vs 8% on placebo; the Wegovy label reports 44% on 2.4 mg vs 16% on placebo. These come from different trial pools, so they are not a direct comparison. SURMOUNT-5 compared the two drugs directly, but its abstract in our sources does not give adverse-event rates.
What did SURPASS-2 show for tirzepatide vs semaglutide in type 2 diabetes?
- SURPASS-2 was a 40-week open-label trial in 1,879 adults with type 2 diabetes on metformin. HbA1c fell by 2.01, 2.24 and 2.30 percentage points with tirzepatide 5, 10 and 15 mg vs 1.86 points with semaglutide 1 mg. Weight loss was greater with tirzepatide by 1.9, 3.6 and 5.5 kg, per the NEJM 2021 abstract.
Can you switch from semaglutide to tirzepatide?
- Neither FDA label gives a conversion table between the two drugs. The Zepbound label says not to use it with other tirzepatide-containing products or with any GLP-1 receptor agonist, which includes semaglutide. Any switch, and which tirzepatide dose to start on, is a decision to make with your prescriber.
How much does tirzepatide cost compared with semaglutide?
- Prices change often, so we keep them on dated pages that quote each manufacturer program directly. See the Zepbound and Mounjaro savings card guides for Lilly's programs and the Wegovy and Ozempic savings card guides for Novo Nordisk's, or estimate a monthly total with the tirzepatide and semaglutide cost tools.
Sources
- Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med 2025;393(1):26-36 (Aronne LJ et al.; PubMed PMID 40353578; doi:10.1056/NEJMoa2416394), Jul 3, 2025. Accessed Oct 19, 2026.
- Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. New England Journal of Medicine (Aronne LJ et al.; PMID 40353578), Jul 3, 2025. Accessed Oct 19, 2026.
- Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med 2021;385(6):503-515 (Frías JP et al.; PubMed PMID 34170647; doi:10.1056/NEJMoa2107519), Aug 5, 2021. Accessed Oct 19, 2026.
- Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387(3):205-216 (Jastreboff AM et al.; PubMed PMID 35658024; doi:10.1056/NEJMoa2206038), Jul 21, 2022. Accessed Oct 19, 2026.
- Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine (Wilding JPH et al.; PMID 33567185), Mar 18, 2021. Accessed Oct 19, 2026.
- Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine (Lincoff AM et al.; PMID 37952131), Dec 14, 2023. Accessed Oct 19, 2026.
- ZEPBOUND (tirzepatide) injection, for subcutaneous use - Full Prescribing Information, Medication Guide and Instructions for Use (DailyMed SPL set ID 487cd7e7-434c-4925-99fa-aa80b1cc776b, version 40). U.S. National Library of Medicine (DailyMed) / Eli Lilly and Company, Aug 28, 2026. Accessed Oct 19, 2026.
- MOUNJARO (tirzepatide) injection, for subcutaneous use - Full Prescribing Information, Medication Guide and Instructions for Use (DailyMed SPL set ID d2d7da5d-ad07-4228-955f-cf7e355c8cc0, version 40). U.S. National Library of Medicine (DailyMed) / Eli Lilly and Company, Aug 27, 2026. Accessed Oct 19, 2026.
- WEGOVY (semaglutide) injection, for subcutaneous use; WEGOVY (semaglutide) tablets, for oral use - Full Prescribing Information (SPL, Revised 6/2026). Novo Nordisk / National Library of Medicine DailyMed, Jun 18, 2026. Accessed Oct 19, 2026.
- OZEMPIC (semaglutide) injection, for subcutaneous use - Full Prescribing Information (SPL). Novo Nordisk / National Library of Medicine DailyMed, Jun 1, 2026. Accessed Oct 19, 2026.
- FDA approves Lilly's Mounjaro™ (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Eli Lilly and Company (investor.lilly.com), May 13, 2022. Accessed Oct 19, 2026.
- FDA Approves New Medication for Chronic Weight Management. U.S. Food and Drug Administration, Nov 8, 2023. Accessed Oct 19, 2026.
- FDA Approves First Medication for Obstructive Sleep Apnea. U.S. Food and Drug Administration, Dec 20, 2024. Accessed Oct 19, 2026.
- Drugs@FDA record NDA209637 (OZEMPIC semaglutide injection) - submissions history. U.S. Food and Drug Administration (openFDA Drugs@FDA API), Oct 19, 2026. Accessed Oct 19, 2026.
- Drugs@FDA record NDA215256 (WEGOVY semaglutide injection) - submissions history. U.S. Food and Drug Administration (openFDA Drugs@FDA API), Oct 19, 2026. Accessed Oct 19, 2026.
- FDA Approves First Treatment to Reduce Risk of Serious Heart Problems Specifically in Adults with Obesity or Overweight. U.S. Food and Drug Administration, Mar 8, 2024. Accessed Oct 19, 2026.
- Novo Nordisk A/S: Wegovy® approved in the US for the treatment of MASH. Novo Nordisk A/S, Aug 15, 2025. Accessed Oct 19, 2026.
- FDA Approves Fourth Product Under National Priority Voucher Program, Higher Dose Semaglutide. U.S. Food and Drug Administration, Mar 19, 2026. Accessed Oct 19, 2026.
- FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. U.S. Food and Drug Administration, Oct 1, 2026. Accessed Oct 19, 2026.
- FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. U.S. Food and Drug Administration, Apr 1, 2026. Accessed Oct 19, 2026.
- Resolution of Tirzepatide Injection Product Shortage and Supply Status (CDER Drug Shortage Staff memorandum). U.S. Food and Drug Administration, Dec 19, 2024. Accessed Oct 19, 2026.
- Declaratory Order: Resolution of Shortages of Semaglutide Injection Products (Ozempic and Wegovy). U.S. Food and Drug Administration, Feb 21, 2025. Accessed Oct 19, 2026.