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In the 72-week SURMOUNT-5 trial of adults with obesity and without type 2 diabetes, tirzepatide produced greater average weight loss than semaglutide. Both commonly caused gastrointestinal side effects, and the trial does not establish an overall safety winner. What you pay depends on your coverage and eligibility; a $50 Medicare copayment applies only to qualifying products under a specific program beginning July 1, 2026.
Which led to more weight loss in the direct comparison?
SURMOUNT-5 was a phase 3b, open-label randomized trial of 751 adults with obesity who did not have type 2 diabetes. Participants received maximum tolerated weekly doses for 72 weeks: tirzepatide at 10 mg or 15 mg, or semaglutide at 1.7 mg or 2.4 mg. These were obesity-treatment doses, so the results should not be generalized without qualification to diabetes-treatment doses or people with different health profiles.
| At week 72 in SURMOUNT-5 | 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 reduction | 18.4 cm | 13.0 cm |
The difference in mean percentage weight change was statistically significant (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 trial was open label and funded by Eli Lilly, and its findings should be understood in that context.
What side effects should you expect?
Gastrointestinal events were the most common side effects reported in both SURMOUNT-5 groups. Most were mild to moderate and occurred primarily during dose escalation. The trial does not support declaring one medicine safer overall based on those findings.
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- AM/PM COMPARTMENTS: Plan doses for morning and evening with separate AM/PM compartments
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Commonly listed symptoms
FDA patient information for Zepbound lists nausea, diarrhea, vomiting, constipation, abdominal pain and other symptoms among common side effects. The Wegovy label also lists gastrointestinal symptoms among common adverse reactions. These label lists are not a head-to-head ranking: they do not show that one treatment causes fewer or less serious side effects than the other.
Compounded products are a separate consideration
The FDA has warned about unapproved compounded semaglutide and tirzepatide products, including dosing and titration concerns and reports of adverse events that may relate to doses beyond approved labeling. Do not treat those products as interchangeable evidence for the approved branded medicines compared in SURMOUNT-5.
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How do the doses and products in the comparison relate to treatment?
The trial compared maximum tolerated weekly doses used for obesity treatment, not every dose or formulation associated with semaglutide or tirzepatide. Its results therefore answer a specific question: how the studied obesity-treatment regimens performed in adults with obesity without type 2 diabetes over 72 weeks.
For the Medicare GLP-1 Bridge’s weight-reduction and maintenance coverage, the listed products include Wegovy injection and tablets, and Zepbound KwikPen. CMS says Zepbound single-dose vials are not included in that program. Product and formulation availability in this benefit should not be taken as evidence that all formulations are covered by other plans or for every indication.
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How much do semaglutide and tirzepatide cost?
There is no single reliable monthly price for everyone. Your out-of-pocket cost depends on the product and formulation, the treatment indication, your location, insurance coverage, plan terms, and eligibility for any assistance or public program. The evidence here does not establish a universal commercial-insurance or cash-pay price; ask your insurer and pharmacy for current, product-specific figures.
A defined Medicare example: the GLP-1 Bridge
Starting July 1, 2026, eligible Part D beneficiaries may receive qualifying drugs through the temporary Medicare GLP-1 Bridge with a $50 monthly copayment. For weight reduction and maintenance, the program lists Wegovy injection or tablets and Zepbound KwikPen, but excludes Zepbound single-dose vials. Eligibility criteria and program rules apply, so this copayment is not a general price for either medicine and does not establish coverage under a commercial plan.
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How should you use this comparison?
SURMOUNT-5 provides a direct efficacy comparison for one defined population and set of doses; it cannot decide which treatment is appropriate for you. A clinician can weigh your diagnosis, health history, potential risks, treatment goals, and coverage when discussing options. Check current FDA-approved labeling and Medicare program rules, since labeling and benefit details can change.
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Product prices and availability are accurate as of the date/time indicated and are subject to change. Any price and availability information displayed on Amazon at the time of purchase will apply.
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