GLP-1 Tirzepatide ReviewIndependent · S.J Partners LLC
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Trial review

SURMOUNT-5: Tirzepatide vs Semaglutide Head to Head

Tirzepatide versus semaglutide, head to head

Direct answer

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 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. That figure belongs to the population, dose, comparator and 72 weeks shown below, and describes a group average under trial conditions rather than a prediction for any individual.

Answer last reviewed: 2026-07-24Evidence:
SURMOUNT-5 at a glanceVerified
DesignPhase 3b, randomised, open-label, active-controlled head-to-head
PopulationAdults 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 size751 randomised 1:1
InterventionTirzepatide once weekly at maximum tolerated dose
ComparatorSemaglutide once weekly at maximum tolerated dose, 1.7 mg or 2.4 mg
Duration72 weeks
Primary endpointPercentage change in body weight from baseline at week 72
Main resultLeast-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
NCT NCT05822830 · DOI 10.1056/NEJMoa2416394Last source check: 2026-07-24
How to read SURMOUNT-5 without over-reading it
1Who was eligibleAdults with obesity but without type 2 diabetes; BMI 30 or above, or 27 or above with at2What they receivedTirzepatide once weekly at maximum tolerated dose3What it was compared againstSemaglutide once weekly at maximum tolerated dose, 1.7 mg or 2.4 mg4For how long72 weeks5What was measured firstPercentage change in body weight from baseline at week 726What the group average wasLeast-squares mean weight change of −20.2% with tirzepatide versus −13.7% with semagluti7What it does not tell youA group average is not a prediction for any individual reader.
Show this figure as a table
StepStageWhat happens
1Who was eligibleAdults 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
2What they receivedTirzepatide once weekly at maximum tolerated dose
3What it was compared againstSemaglutide once weekly at maximum tolerated dose, 1.7 mg or 2.4 mg
4For how long72 weeks
5What was measured firstPercentage change in body weight from baseline at week 72
6What the group average wasLeast-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
7What it does not tell youA group average is not a prediction for any individual reader.
Strip any step and the result stops meaning what the trial found.
Primary results, from the peer-reviewed publicationNew England Journal of Medicine 2025;393(1):26-36
Tirzepatide, % weight change20%Semaglutide, % weight change14%
Show this figure as a table
ItemWeight changeEvidence
Tirzepatide, % weight change20%Verified
Semaglutide, % weight change14%Verified
Group means under trial conditions. Not a prediction for any individual reader.
What this trial can and cannot tell you
QuestionPosition
Average effect in the studied populationReported once captured
Your individual outcomeNot predicted by any trial
Effect of a compounded preparationNot studied here
Effect at doses outside the protocolNot studied here
Effect after stoppingOnly if the trial included a withdrawal phase
Long-term safety beyond the trialOutside the observation window

Who was studied

342 words · unwritten
  • Inclusion and exclusion criteria in plain language. Say who was not studied — that is usually the more useful half.

What was given, and what it was compared against

342 words · unwritten
  • Dose, titration schedule, comparator, and whether the comparator was placebo or an active drug.

Results

342 words · unwritten
  • Primary endpoint first, with absolute numbers alongside percentages. Secondary endpoints labelled as secondary.

Adverse events and discontinuations

342 words · unwritten
  • Never omitted for length. Report discontinuation rates alongside efficacy.

Limitations

342 words · unwritten
  • Funding, blinding, dropout handling, generalisability, duration.

How this should and should not be read

342 words · unwritten
  • Explicitly address the misreadings this trial commonly attracts.

How it compares with other trials

342 words · unwritten
  • Only where designs are comparable. Say so when they are not.
Before publish — primary-source capture
  • Retrieve the registry record and the peer-reviewed publication. Record NCT, DOI and PMID.
  • Do not summarise from a manufacturer press release, a conference abstract described as a result, or a news article.
  • Where only topline or preprint data exists, label it as such everywhere it appears, including the direct answer.
  • Medical review is mandatory on this page before publication.

Questions readers actually ask

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.

Cite this pageCC BY 4.0

GLP-1 Tirzepatide Review. “SURMOUNT-5: Tirzepatide vs Semaglutide Head to Head.” S.J Partners LLC, 2026-07-24. https://glp1tirzepatidereview.com/research/surmount-5/

When quoting a figure, include the capture date shown beside it rather than the date you read this page. A price without its capture date is not a usable citation.

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