In a 72-week head-to-head trial of adults with obesity but without type 2 diabetes, tirzepatide produced greater average weight loss than semaglutide at the obesity-treatment doses studied. Both medicines commonly caused gastrointestinal side effects, and the trial does not establish that one is safer overall. Cost depends on coverage and eligibility; a $50 monthly Medicare copayment applies only to qualifying beneficiaries and products under the temporary GLP-1 Bridge beginning July 1, 2026.
How much weight did participants lose?
The phase 3b SURMOUNT-5 trial randomly assigned 751 adults with obesity and without type 2 diabetes to weekly tirzepatide or semaglutide. It was open-label, meaning participants and researchers knew which treatment was being used. Participants received the maximum tolerated doses studied for obesity treatment: tirzepatide 10 mg or 15 mg, or semaglutide 1.7 mg or 2.4 mg, for 72 weeks.
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| Outcome at week 72 | Tirzepatide | Semaglutide |
|---|---|---|
| Mean percentage change in body weight | −20.2% (95% CI, −21.4 to −19.1) | −13.7% (95% CI, −14.9 to −12.6) |
| Mean waist change | −18.4 cm | −13.0 cm |
| Weekly doses tested | 10 mg or 15 mg | 1.7 mg or 2.4 mg |
The difference in mean weight change was 6.5 percentage points in favor of tirzepatide; the trial reported P<0.001. The investigators concluded that tirzepatide was superior for reducing body weight and waist circumference in this study population. These are group averages, not a prediction of what any one person will lose. The findings apply to the trial’s participants and obesity-treatment doses, not automatically to people with type 2 diabetes or to different doses. The study was funded by Eli Lilly, the maker of tirzepatide.
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Gastrointestinal effects were the most common adverse events in both SURMOUNT-5 groups. Most were mild to moderate and occurred primarily while doses were being increased. This does not mean everyone will have them, or that symptoms will be the same for each person.
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FDA patient information for Zepbound lists nausea, diarrhea, vomiting, constipation, abdominal pain and other symptoms among common side effects. The Wegovy prescribing information also lists gastrointestinal symptoms among common adverse reactions. These label lists describe each medicine separately; they are not a head-to-head ranking of total side-effect risk. The trial evidence summarized here does not establish an overall safety winner.
Ask the prescriber what symptoms warrant a call, how dose increases are managed, and what to do if side effects interfere with eating, drinking, or taking the medicine as directed. FDA has also cautioned consumers about unapproved compounded semaglutide and tirzepatide products, including dosing and titration problems and adverse-event reports that may involve doses beyond approved labeling. Compounded products should not be treated as interchangeable evidence for the approved products compared in SURMOUNT-5.
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Which products and doses are being compared?
The comparison is between semaglutide and tirzepatide used at the maximum tolerated obesity-treatment doses studied in SURMOUNT-5. The FDA-approved product context matters: the Medicare GLP-1 Bridge lists Wegovy injection and tablets for weight reduction and maintenance, and Zepbound KwikPen. The trial’s weekly injectable doses should not be read as a comparison of every formulation or of products prescribed for other indications.
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How much do semaglutide and tirzepatide cost?
There is no single price that applies to everyone. A person’s out-of-pocket cost depends on the specific product and formulation, the reason it is prescribed, insurance coverage, eligibility rules, and pharmacy terms. The evidence available here does not establish a general cash price or a typical commercial-insurance copay; check the current amount with the insurer and pharmacy for the exact product and prescription.
Medicare GLP-1 Bridge
Medicare.gov describes a temporary GLP-1 Bridge beginning July 1, 2026. Eligible Part D beneficiaries may pay a $50 monthly copayment for specified qualifying drugs. For weight reduction and maintenance, the listed products include Wegovy injection and tablets and Zepbound KwikPen. CMS says Zepbound single-dose vials are not included. Eligibility and program rules apply, so the $50 copayment is not a general monthly price or a guarantee of coverage for an individual.
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What should guide a treatment decision?
The trial offers a direct comparison for one specific population, but it cannot settle an individual treatment choice. Discuss the following with a qualified clinician and, where relevant, the health plan:
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- Whether the person’s diagnosis and treatment goals match an approved use.
- Which formulation and dose are appropriate, and how dose increases will be handled.
- Relevant health history, potential risks, and how side effects would be monitored.
- The person’s actual coverage, eligibility, and expected out-of-pocket cost for the named product.
For clinical context, SURMOUNT-5 was an open-label 2025 trial funded by Eli Lilly. Its result is evidence of greater average weight reduction with tirzepatide in that study—not a guarantee for an individual or a comparison across every population, dose, and formulation.
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