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For adults with obesity who do not have type 2 diabetes, tirzepatide led to greater average weight loss than semaglutide in the 72-week SURMOUNT-5 trial: 20.2% versus 13.7% of body weight. That open-label trial tested specific maximum-tolerated doses; it does not predict an individual’s result or compare every current formulation. In particular, it did not test Wegovy HD, the 7.2 mg semaglutide injection FDA approved in March 2026 for certain adults.
What SURMOUNT-5 found—and what it did not
Published in the New England Journal of Medicine in 2025, SURMOUNT-5 randomized 751 adults with obesity but without type 2 diabetes to weekly injections of maximum-tolerated tirzepatide or semaglutide for 72 weeks. Participants received tirzepatide 10 mg or 15 mg, or semaglutide 1.7 mg or 2.4 mg. The trial was phase 3b, controlled, and open-label, meaning participants and clinicians knew which treatment was being used.
At week 72, the least-squares mean change in body weight was −20.2% with tirzepatide (95% confidence interval, −21.4% to −19.1%) and −13.7% with semaglutide (95% confidence interval, −14.9% to −12.6%); the difference was statistically significant (P<0.001). The difference between those reported averages is 6.5 percentage points. These are group averages, not a promised amount of weight loss for any one person.
The result applies to the population and dose regimens studied. It does not establish which medicine works better for a particular person, settle the comparison for people with type 2 diabetes, or compare tirzepatide with Wegovy HD 7.2 mg. Wegovy HD was approved after the trial’s comparison and was not one of its study doses.
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1Clear out junk files and repair common Windows errors2Scan for outdated or missing drivers - takes under a minute3Repair Windows errors before they cause bigger problemsHow semaglutide and tirzepatide differ
Semaglutide activates the GLP-1 receptor. Tirzepatide activates both the GIP and GLP-1 receptors. In the United States, the brand and formulation matter: a medicine’s weight-management indication is not interchangeable with the labeling for a diabetes product containing the same active ingredient.
| Comparison | Semaglutide | Tirzepatide |
|---|---|---|
| Receptor activity | GLP-1 receptor agonist (FDA Wegovy prescribing information) | GIP and GLP-1 receptor agonist (FDA Zepbound approval announcement) |
| U.S. weight-management brand | Wegovy; FDA-approved uses include long-term weight reduction and maintenance for eligible patients, alongside reduced-calorie eating and increased physical activity. Wegovy has additional specific labeled uses (FDA 2025 prescribing information). | Zepbound; 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 (FDA approval announcement). |
| Diabetes-product distinction | Ozempic is a separate branded product with its own formulation, dose, and indication; do not treat its labeling as identical to Wegovy’s. | Mounjaro is the diabetes product FDA distinguished from Zepbound; FDA approved Mounjaro for blood-sugar control in adults with type 2 diabetes. |
| Regimens compared in SURMOUNT-5 | Maximum-tolerated 1.7 mg or 2.4 mg weekly injection | Maximum-tolerated 10 mg or 15 mg weekly injection |
In March 2026, FDA approved Wegovy HD, a 7.2 mg semaglutide injection, for long-term weight reduction and maintenance in certain adults. Because that approval came after SURMOUNT-5, the trial’s semaglutide result should not be presented as a direct comparison against Wegovy HD. Confirm the current full prescribing information and availability with a clinician or pharmacist.
Rank #2
- Made in USA - Proudly produced in Ohio by a Veteran-owned business
- Comprehensive Tracking: This log book provides dedicated sections to track daily and weekly health metrics, including weight, diet, exercise, and medication side effects.
- Detailed Personal Records: Keep a thorough record of your health conditions, allergies, and GLP-1 medication specifics, such as the starting date, dosage, and injection schedule.
- Goal-Oriented Features: The log book helps you stay motivated by allowing you to record personal motivations, exercise goals, and track your progress with starting and ending weight and waist circumference measurements.
- Reorder SKU: LOG-104-M3CW-PP(GLP-1)
Side effects and safety questions
The head-to-head weight-loss result does not by itself show which drug has worse side effects. Safety and tolerability depend on the person, dose, medical history, and the specific product label. Both choices require a review of relevant health conditions, other medicines, prior treatment response, and dose tolerance with a qualified clinician.
Wegovy’s prescribing information carries a boxed warning because semaglutide caused thyroid C-cell tumors in rodents; whether that finding applies to humans is unknown. Wegovy is contraindicated for people with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2). Its full prescribing information describes gastrointestinal and other risks that should be reviewed before treatment.
Rank #3
- Made in USA - Proudly produced in Ohio by a Veteran-owned business
- Comprehensive Tracking: This log book provides dedicated sections to track daily and weekly health metrics, including weight, diet, exercise, and medication side effects.
- Detailed Personal Records: Keep a thorough record of your health conditions, allergies, and GLP-1 medication specifics, such as the starting date, dosage, and injection schedule.
- Goal-Oriented Features: The log book helps you stay motivated by allowing you to record personal motivations, exercise goals, and track your progress with starting and ending weight and waist circumference measurements.
- Reorder SKU: LOG-104-69CW-PP(GLP-1)
In January 2026, FDA reported that its review found no increased risk of suicidal ideation or behavior for the GLP-1 receptor agonists it reviewed and requested removal of the relevant warning from applicable labels. Label wording can change; check the current prescribing information for the exact medicine being considered.
How to compare the options with a clinician
The trial result is one useful input, not a treatment recommendation for everyone. A practical discussion should identify the exact product and health goal before comparing expected benefits or risks.
- Match the indication to the goal. Confirm whether the aim is chronic weight management, blood-sugar control, or another labeled use. Check the current U.S. prescribing information for the proposed brand.
- Account for health history. Discuss diabetes status, other conditions, contraindications, precautions, and all medicines or supplements being taken.
- Review past treatment experience. Bring up any prior use, degree of response, adverse effects, and doses that were or were not tolerated.
- Specify the product and regimen. Confirm brand, formulation, dose, and route rather than relying on the generic drug name alone.
- Plan for continuity. Consider coverage, access, and the ability to continue the prescribed treatment; these vary by payer, place, product, dose, and date.
- Include personal preference. Injection routine, treatment priorities, and willingness to manage potential adverse effects are part of an individualized decision.
Can you switch from semaglutide to tirzepatide?
A switch may be something to discuss with the prescribing clinician, but SURMOUNT-5 did not test a switching strategy. The study compared people assigned to one treatment regimen with people assigned to the other; it does not provide a universal conversion dose or schedule. Do not stop, combine, or change doses on your own. The clinician should decide whether a switch is appropriate and give product-specific instructions based on the current labels and your treatment history.
Independent reader supportYour contribution helps us test, update, and keep practical guides available for everyone.Why compounded versions are not the same as approved products
FDA says compounded drugs are not FDA-approved and are not reviewed by the agency for safety, effectiveness, or quality before marketing. FDA says compounding should be used only when a patient’s medical needs cannot be met by an FDA-approved drug. It has also warned that semaglutide sodium and semaglutide acetate are different active ingredients from those in approved medicines. A compounded preparation should not be assumed to be equivalent to Wegovy, Ozempic, Zepbound, or Mounjaro.
What is not settled by the comparison
SURMOUNT-5 does not establish a universal winner for every patient, nor does it answer how the treatments compare across all doses, formulations, health conditions, or time horizons. The trial directly supports an average weight-loss comparison for adults with obesity without type 2 diabetes using the studied maximum-tolerated regimens over 72 weeks. Current prices, insurance coverage, and local availability are not comparable fixed values and should be checked for the specific product and location.
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