Trial review
SURMOUNT-5: The drug vs Semaglutide Head to Head
This medicine versus semaglutide, head to head
SURMOUNT-5 was a phase 3b, randomised, open-label, active-controlled head-to-head funded by Eli Lilly and Company. Least-squares mean weight change of −20.2% with the active ingredient versus −13.7% with semaglutide (P<0.001); −22.8 kg versus −15.0 kg; waist circumference −18.4 cm versus −13.0 cm.
| Design | Phase 3b, randomised, open-label, active-controlled head-to-head |
|---|---|
| Population | Adults with obesity but without type 2 diabetes; BMI 30 or above, or 27 or above with at least one obesity-related complication. 32 sites in the United States and Puerto Rico, April 2023 to November 2024 |
| Sample size | 751 randomised 1:1 |
| Intervention | The molecule once weekly at maximum tolerated dose |
| Comparator | Semaglutide once weekly at maximum tolerated dose, 1.7 mg or 2.4 mg |
| Duration | 72 weeks |
| Primary endpoint | Percentage change in body weight from baseline at week 72 |
| Main result | Least-squares mean weight change of −20.2% with this GLP-1 versus −13.7% with semaglutide (P<0.001); −22.8 kg versus −15.0 kg; waist circumference −18.4 cm versus −13.0 cm |
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| Step | Stage | What happens |
|---|---|---|
| 1 | Who was eligible | Adults with obesity but without type 2 diabetes; BMI 30 or above, or 27 or above with at least one obesity-related complication. 32 sites in the United States and Puerto Rico, April 2023 to November 2024 |
| 2 | What they received | This medicine once weekly at maximum tolerated dose |
| 3 | What it was compared against | Semaglutide once weekly at maximum tolerated dose, 1.7 mg or 2.4 mg |
| 4 | For how long | 72 weeks |
| 5 | What was measured first | Percentage change in body weight from baseline at week 72 |
| 6 | What the group average was | Least-squares mean weight change of −20.2% with tirzepatide versus −13.7% with semaglutide (P<0.001); −22.8 kg versus −15.0 kg; waist circumference −18.4 cm versus −13.0 cm |
| 7 | What it does not tell you | A group average is not a prediction for any individual reader. |
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| Item | Weight change | Evidence |
|---|---|---|
| Tirzepatide, % weight change | 20% | Verified |
| Semaglutide, % weight change | 14% | Verified |
| Question | Position |
|---|---|
| Average effect in the studied population | Reported once captured |
| Your individual outcome | Not predicted by any trial |
| Effect of a compounded preparation | Not studied here |
| Effect at doses outside the protocol | Not studied here |
| Effect after stopping | Only if the trial included a withdrawal phase |
| Long-term safety beyond the trial | Outside the observation window |
Who was studied?
Adults with obesity but without type 2 diabetes; BMI 30 or above, or 27 or above with at least one obesity-related complication. 32 sites in the United States and Puerto Rico, April 2023 to November 2024
Registry and publication identifiers: NCT05822830 · DOI 10.1056/NEJMoa2416394. Sponsor: Eli Lilly and Company. Checked against the source on 2026-08-03.
What was given, and what was it compared against?
| Field | What the record states |
|---|---|
| Design | Phase 3b, randomised, open-label, active-controlled head-to-head |
| Intervention | Tirzepatide once weekly at maximum tolerated dose |
| Dose | 10 mg or 15 mg |
| Comparator | Semaglutide once weekly at maximum tolerated dose, 1.7 mg or 2.4 mg |
| Duration | 72 weeks |
| Primary endpoint | Percentage change in body weight from baseline at week 72 |
This was not a placebo comparison. An active comparator answers whether the drug is at least as good as one already shown to work, which supports a weaker claim than a placebo-controlled reduction. Coverage that reports both in the same words is flattening a real difference in evidence.
What did it find?
Least-squares mean weight change of −20.2% with tirzepatide versus −13.7% with semaglutide (P<0.001); −22.8 kg versus −15.0 kg; waist circumference −18.4 cm versus −13.0 cm
A trial result is a mean across a population, not a prediction for an individual. The same trial that produces an average contains people who did far better and people who did not respond, and a page quoting only the average is quoting the part that flatters it.
What were the adverse events and discontinuations?
Most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 4.8% of the tirzepatide group and 3.5% of the semaglutide group
Six participants in each group discontinued because of adverse events Discontinuation matters commercially as well as clinically: it concentrates during titration, which is the same window a prepaid multi-month plan commits a patient through. Ask what is refunded before prepaying.
What are the limitations?
Open-label, so neither participants nor investigators were blinded. Industry-funded. Compares maximum tolerated doses, not fixed doses, and more semaglutide participants reached their top dose than tirzepatide participants in some real-world analyses. Excludes people with type 2 diabetes.
How should this be read, and how should it not?
- It describes the product that was studied. Every figure here was collected on the FDA-approved product. No compounded preparation has a trial of its own, and no figure on this page transfers to one.
- It describes the dose that was studied. A microdose sits below the range trialled here, so no result on this page applies to one at any price.
- It describes the population that was studied. A result in people with established cardiovascular disease does not transfer to primary prevention, and a result in diabetes does not transfer to weight management.
- It is not a dosing instruction. Your prescriber sets your regimen.
How does it compare with the other trials on this site?
| Trial | Intervention | Reported result | Duration |
|---|---|---|---|
| SURMOUNT-5 | Tirzepatide once weekly at maximum | Least-squares mean weight change of −20.2% with tirzepatide versus −13.7% with semaglutide | 72 weeks |
| ATTAIN-1 | Orforglipron, once-daily oral non- | Approximately 11% to 12.4% mean weight reduction at the highest dose over 72 weeks. Lilly | 72 weeks |
| OASIS 4 | Oral semaglutide 25 mg once daily, | 13.6% mean weight reduction on the treatment-policy estimand versus 2.2% placebo; 16.6% ve | 64 weeks of treatment |
| SELECT | Semaglutide | Approximately a 20% relative reduction in the primary composite; event rate fell from roug | Mean follow-up approxi |
| STEP-1 | Semaglutide | Mean weight change of −14.9% against −2.4% on placebo; about 86% reached 5% or more, about | 68 weeks |
| STEP-8 | Semaglutide 2.4 mg weekly | Mean weight change approximately −15.8% on semaglutide against approximately −6.4% on lira | 68 weeks |
| SUMMIT | Tirzepatide once weekly at maximum | A 38% reduction in the combined endpoint of cardiovascular death and worsening heart-failu | 52 weeks to the sympto |
| SURMOUNT-1 | Tirzepatide once weekly | Treatment-regimen estimand: −15.0% (5 mg), −19.5% (10 mg), −20.9% (15 mg) versus −3.1% pla | 72 weeks |
| SURMOUNT-1, three-year prediabetes analysis | Tirzepatide once weekly | Three years of tirzepatide produced substantial sustained weight reduction and a markedly | 176 weeks of treatment |
| SURMOUNT-3 | not stated | −18.4% additional reduction versus +2.5% with placebo, on top of lead-in weight loss | 72 weeks |
Separate trials with different populations, durations and endpoints. Only a head-to-head supports a direct comparison between two drugs; the rest sit side by side here for reference, not for subtraction.
Frequently asked questions
Does this mean I would lose that much weight?
No. Trials report group averages under controlled conditions with specific eligibility criteria. Individual results vary widely, and the trial population may not resemble you.
Do these results apply to compounded tirzepatide?
Not automatically. Trials studied the approved product at studied doses. A compounded preparation at a different concentration, formulation or route has not been through those trials.
Related on this site
- Research hubResearch
- SURMOUNT-1 Tirzepatide Trial ExplainedResearch
- SURMOUNT-3 Tirzepatide Trial ExplainedResearch
- SURMOUNT-4: Weight Maintenance and Tirzepatide WithdrawalResearch
- How rankings are computedCore & Trust
- All-in cost toolTools
- Price records, machine-readableData
- Tirzepatide Clinical Trial FinderTools
- SURPASS-2: Tirzepatide vs Semaglutide in Type 2 DiabetesResearch
- SURMOUNT-OSA and Tirzepatide for Sleep ApneaResearch
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- SURMOUNT-4: Weight Maintenance and Tirzepatide Withdrawal
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GLP-1 Semaglutide Rx. “SURMOUNT-5: Tirzepatide vs Semaglutide Head to Head.” S.J Partners LLC, 2026-08-03. https://glp1semaglutiderx.com/research/surmount-5/
Quote the capture date beside a figure, not the date you read this page. Why.