In a 72-week head-to-head trial of adults with obesity who did not have type 2 diabetes, tirzepatide led to greater average weight loss than semaglutide: 20.2% versus 13.7%. That result applies to the doses and people studied; it does not predict an individual’s result or compare tirzepatide with the higher-dose Wegovy HD approved later.
What the head-to-head trial found
The phase 3b SURMOUNT-5 trial randomly assigned 751 adults with obesity and without type 2 diabetes in a 1:1 ratio to weekly injections of maximum-tolerated tirzepatide or maximum-tolerated semaglutide for 72 weeks. The study was open-label, meaning participants and clinicians knew which treatment was being used.
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| Trial treatment | Maximum-tolerated doses studied | Average body-weight change at week 72 |
|---|---|---|
| Tirzepatide | 10 mg or 15 mg weekly | −20.2% (95% confidence interval, −21.4% to −19.1%) |
| Semaglutide | 1.7 mg or 2.4 mg weekly | −13.7% (95% confidence interval, −14.9% to −12.6%) |
The difference in average weight change was statistically significant (P<0.001). These are least-squares mean results reported in the New England Journal of Medicine in 2025, not a promise that a particular person will lose that amount. Individual results can differ.
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The finding favors tirzepatide over the semaglutide doses tested for average weight reduction in this trial population. Because the trial excluded people with type 2 diabetes, it does not establish which medicine produces more weight loss for people with diabetes. Its open-label design and specific dose regimens also limit how broadly the result can be applied.
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In March 2026, the FDA approved Wegovy HD, a 7.2 mg semaglutide injection for long-term weight reduction and maintenance in certain adults. That dose was not included in SURMOUNT-5, so the trial is not a direct comparison of tirzepatide with Wegovy HD. Check the current prescribing information for the full eligibility criteria and product details.
Semaglutide and tirzepatide are different medicines
Both are injectable medicines used in weight management, but they act on different hormone pathways and their brands, doses, and FDA-labeled uses are not interchangeable. The following distinctions describe U.S. labeling; the exact product and indication matter.
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| Medicine | How it works | Relevant U.S. brand and labeling distinction |
|---|---|---|
| Semaglutide | GLP-1 receptor agonist | Wegovy is labeled for long-term weight reduction and maintenance in eligible people, alongside reduced-calorie eating and increased physical activity. Its FDA label also includes other specific uses. Ozempic is a distinct branded product; do not assume its labeling, dose, or formulation is the same as Wegovy’s. |
| Tirzepatide | Activates both GIP and GLP-1 receptors | Zepbound is FDA-approved for chronic weight management in adults with obesity, or overweight with at least one weight-related condition, alongside reduced-calorie eating and increased physical activity. Mounjaro is labeled for blood-sugar control in adults with type 2 diabetes; it is not simply another name for Zepbound. |
For either medicine, a brand name alone is not enough to identify the right comparison. Confirm the product, formulation, dose, route, and reason it is prescribed. The FDA’s Wegovy label cited here is dated 2025, and prescribing information can change; consult the current label for the product being considered.
Safety and prescribing considerations
These medicines require a clinician’s assessment, including a review of medical history, other medicines, treatment goals, and the product’s prescribing information. For Wegovy, the boxed warning concerns thyroid C-cell tumors observed in rodents; whether this risk applies to humans is unknown. Wegovy is contraindicated for people with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2 (MEN 2). Its full label describes additional risks and precautions.
FDA safety communications and product labels may be updated. For example, in January 2026 the FDA reported no increased risk of suicidal ideation or behavior for the GLP-1 receptor agonists it reviewed and asked for the relevant warning to be removed from applicable labels. Check the current label rather than relying on older warning language.
Do not assume compounded versions are equivalent
Compounded drugs are not FDA-approved, and the FDA does not review them for safety, effectiveness, and quality before they are marketed. The agency says compounding should be used only when a patient’s medical needs cannot be met by an FDA-approved drug. Semaglutide sodium and semaglutide acetate are different active ingredients from the semaglutide in approved medicines. A compounded preparation should not be treated as an equivalent substitute for a branded, FDA-approved product.
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How to discuss which option fits your situation
The trial result is one factor, not an individual prescribing decision. Bring these questions to the clinician managing your care:
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1Fix the driver behind crashes, sound loss and screen glitches2Repair Windows errors before they cause bigger problems3Scan for outdated or missing drivers - takes under a minute- What is the treatment goal and labeled indication? Clarify whether the prescription is for chronic weight management, diabetes treatment, or another labeled use.
- How does my health history affect the choice? Review diabetes status, other conditions, contraindications, precautions, and all current medicines.
- How did I respond to previous treatment? Discuss prior weight change, side effects, and whether you tolerated the dose reached.
- Which exact product and regimen are being considered? Confirm brand, formulation, dose, and injection schedule instead of comparing drug names in isolation.
- Can I obtain and continue the prescribed treatment? Insurance coverage, access, and availability vary by product, dose, payer, location, and date. Check directly with your insurer, pharmacy, and clinician; there is no single cost comparison that applies to everyone.
- What do I prefer and feel able to follow? Discuss practical fit and preferences alongside expected benefits and risks.
Can you switch from semaglutide to tirzepatide?
A clinician may consider a change, but there is no one-size-fits-all conversion based on the trial’s weight-loss averages. Do not take both medicines together or choose a starting dose yourself. Ask the prescriber to set the timing and dose for your circumstances, taking account of the exact product, current dose, last injection, treatment response, side effects, and other health conditions. If access or a supply interruption is driving the change, contact the prescriber before adjusting or restarting treatment.
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