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Tirzepatide vs semaglutide: the head-to-head trial and the labels

Updated Sep 27, 2026. Numbers in brackets link to the source each fact comes from.

In the one trial that put them side by side for weight loss, tirzepatide (Zepbound) led to more weight loss than semaglutide (Wegovy). In SURMOUNT-5, people on tirzepatide lost 20.2% of their body weight on average at 72 weeks, against 13.7% on semaglutide [2]. Both drugs worked, both mostly caused stomach and gut side effects, and the trial was funded by the company that makes tirzepatide.

What SURMOUNT-5 tested

The trial enrolled adults with obesity who did not have type 2 diabetes. They were randomly assigned to weekly shots of tirzepatide at the highest dose they could tolerate (10 or 15 mg) or semaglutide at the highest dose they could tolerate (1.7 or 2.4 mg), for 72 weeks [1]. It was open-label, meaning participants and staff knew which drug each person was taking [1]. A total of 751 people were randomized [2].

Result at 72 weeks Tirzepatide Semaglutide
Average change in body weight -20.2% -13.7% [2]
Average change in waist size -18.4 cm -13.0 cm [3]

People on tirzepatide were also more likely to reach each weight-loss milestone the trial tracked: at least 10%, 15%, 20% and 25% of body weight [4]. In both groups, the most common side effects were stomach and gut problems, mostly mild to moderate and mostly while the dose was being raised [5].

How to read the result

  • It is an average. Some people on each drug lost much more and some much less. The trial cannot tell you which group you would fall into.
  • It compared top doses only. Everyone aimed for the highest dose they could tolerate, so the trial says nothing direct about lower doses.
  • It left out diabetes. People with type 2 diabetes were not enrolled [1].
  • The sponsor makes one of the drugs. Eli Lilly funded SURMOUNT-5 [6], and Lilly markets Zepbound [7].

An earlier head-to-head trial, SURPASS-2, was done in people with type 2 diabetes and was also funded by Eli Lilly [29] [30]. It compared three tirzepatide doses (5, 10 and 15 mg) with semaglutide 1 mg for 40 weeks in 1,879 people [25]. Weight loss was greater on every tirzepatide dose, by 1.9 kg, 3.6 kg and 5.5 kg on average [26]. Rates of gut side effects were similar: nausea in 17% to 22% on tirzepatide and 18% on semaglutide, diarrhea in 13% to 16% and 12%, and vomiting in 6% to 10% and 8% [27].

For the placebo-controlled results of each drug on its own, see weight-loss results.

How the two molecules work

Tirzepatide acts on two hormone receptors, GIP and GLP-1 [8]. Semaglutide acts on the GLP-1 receptor only [9]. The trials compared the two drugs as a whole; they did not test which receptor accounts for the difference in weight loss.

How the labels differ

Each molecule is sold under more than one brand. Zepbound and Wegovy are the weight-management versions; Mounjaro (tirzepatide) and Ozempic (semaglutide) are labeled for type 2 diabetes [14] [15].

Zepbound (tirzepatide) Wegovy (semaglutide)
Other approved uses Moderate to severe sleep apnea in adults with obesity [10] Lowering heart attack and stroke risk in adults with heart disease and excess weight [11]; a liver disease called MASH with fibrosis [13]
Teens Not studied; the guide says safety and effectiveness in children are not known [28] Ages 12 and older with obesity [12]
Starting dose 2.5 mg weekly for 4 weeks [16] 0.25 mg weekly [18]
Maintenance dose for weight 5, 10 or 15 mg weekly [17] 1.7 or 2.4 mg weekly [19], up to 7.2 mg for some patients [20]
Pill version None Wegovy tablets, 25 mg daily for maintenance [21]

Both labels carry the same boxed warning about thyroid C-cell tumors seen in rodents [22] [23]. Neither drug is meant to be combined with another GLP-1 medicine; the Zepbound label says so directly [24]. Neither label gives a way to convert a dose of one molecule into the other, so switching means a new dose plan from your prescriber. For step-by-step schedules, see dosing, and for every side-effect rate on each label, see Zepbound and Wegovy.

Which one costs less

Neither molecule has one price. What you pay depends on the brand, the dose, whether insurance covers it, and where you buy. Compare current prices for both in our price table, read how the main cash options work in GLP-1 cost without insurance, and check the terms of each seller on the program pages.

Which drug fits you depends on your health history, other conditions, how you tolerate each one, and what you can get covered. The trial results are a starting point for that conversation with your prescriber, not a verdict.

Sources

  1. In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) subcutaneously once weekly for 72 weeks. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  2. A total of 751 participants underwent randomization. The least-squares mean percent change in weight at week 72 was -20.2% (95% confidence interval [CI], -21.4 to -19.1) with tirzepatide and -13.7% (95% CI, -14.9 to -12.6) with semaglutide (P<0.001). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  3. The least-squares mean change in waist circumference was -18.4 cm (95% CI, -19.6 to -17.2) with tirzepatide and -13.0 cm (95% CI, -14.3 to -11.7) with semaglutide (P<0.001). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  4. Participants in the tirzepatide group were more likely than those in the semaglutide group to have weight reductions of at least 10%, 15%, 20%, and 25%. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  5. The most common adverse events in both treatment groups were gastrointestinal, and most were mild to moderate in severity and occurred primarily during dose escalation. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  6. (Funded by Eli Lilly; SURMOUNT-5 ClinicalTrials.gov number, NCT05822830.). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  7. Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA dailymed.nlm.nih.gov, read Sep 27, 2026.
  8. Tirzepatide is a GIP receptor and GLP-1 receptor agonist. dailymed.nlm.nih.gov, read Sep 27, 2026.
  9. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. dailymed.nlm.nih.gov, read Sep 27, 2026.
  10. to treat moderate to severe obstructive sleep apnea (OSA) in adults with obesity. dailymed.nlm.nih.gov, read Sep 27, 2026.
  11. to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV disease and either obesity or overweight. dailymed.nlm.nih.gov, read Sep 27, 2026.
  12. adults and pediatric patients aged 12 years and older with obesity. dailymed.nlm.nih.gov, read Sep 27, 2026.
  13. for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults. dailymed.nlm.nih.gov, read Sep 27, 2026.
  14. as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. dailymed.nlm.nih.gov, read Sep 27, 2026.
  15. as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. dailymed.nlm.nih.gov, read Sep 27, 2026.
  16. The recommended starting dosage of ZEPBOUND for all indications is 2.5 mg injected subcutaneously once weekly for 4 weeks. dailymed.nlm.nih.gov, read Sep 27, 2026.
  17. Weight Reduction and Long-Term Maintenance: 5 mg, 10 mg, or 15 mg injected subcutaneously once weekly. (2.2) dailymed.nlm.nih.gov, read Sep 27, 2026.
  18. The recommended starting dosage of WEGOVY injection is 0.25 mg administered subcutaneously once weekly. dailymed.nlm.nih.gov, read Sep 27, 2026.
  19. The maintenance dosage of WEGOVY for weight reduction in adults is either 1.7 mg or 2.4 mg (recommended) injected subcutaneously once weekly. dailymed.nlm.nih.gov, read Sep 27, 2026.
  20. For patients who tolerate the 2.4 mg dosage for at least 4 weeks and additional weight reduction is clinically indicated, the dosage may be increased to a maximum dosage of 7.2 mg subcutaneously once weekly. dailymed.nlm.nih.gov, read Sep 27, 2026.
  21. The recommended maintenance dosage of WEGOVY tablets is 25 mg orally once daily. dailymed.nlm.nih.gov, read Sep 27, 2026.
  22. WARNING: RISK OF THYROID C-CELL TUMORS dailymed.nlm.nih.gov, read Sep 27, 2026.
  23. WARNING: RISK OF THYROID C-CELL TUMORS dailymed.nlm.nih.gov, read Sep 27, 2026.
  24. ZEPBOUND contains tirzepatide. Coadministration with other tirzepatide-containing products or with any glucagon-like peptide-1 (GLP-1) receptor agonist is not recommended. dailymed.nlm.nih.gov, read Sep 27, 2026.
  25. In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  26. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  27. The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  28. It is not known if ZEPBOUND is safe and effective for use in children. dailymed.nlm.nih.gov, read Sep 27, 2026.
  29. In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  30. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.

This page reports what official sources say; it is not medical advice. Medical disclaimer.