Clinical research

SURMOUNT-5: Tirzepatide versus semaglutide, head to head

Phase 3b, randomised, open-label, active-controlled head-to-head. 751 randomised 1:1, over 72 weeks. Sponsor: Eli Lilly and Company.

SURMOUNT-5 (NCT05822830) tested tirzepatide once weekly at maximum tolerated dose at 10 mg or 15 mg against semaglutide once weekly at maximum tolerated dose, 1.7 mg or 2.4 mg in 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.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 Primary source linked: the source is a citable peer-reviewed / registry record, which we have not independently re-extracted from the full paper in this session.

Study design

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 (10 mg or 15 mg)
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
SponsorEli Lilly and Company

Results

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

Reported change by arm (chart data rendered as a table for accessibility)
ArmReported change
Tirzepatide, % weight change20.2%
Semaglutide, % weight change13.7%

Adverse events & 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

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.

Practical interpretation

This is one trial, reported by Eli Lilly and Company, read directly against the registry and publication linked below — GLP Ranked has not re-run the statistics or obtained the patient-level data. Results describe group averages under trial conditions and may not describe any individual's outcome, including with a compounded, non-FDA-approved version of a similar active ingredient. Always check the primary source before citing a specific number.

Sources

  1. New England Journal of Medicine 2025;393(1):26-36 — Peer-reviewed publication
  2. SURMOUNT-5 — ClinicalTrials.gov record NCT05822830 — Trial registry record

Cite this page

GLP Ranked. "SURMOUNT-5: Tirzepatide versus semaglutide, head to head." Updated 2026-07-24. https://glpranked.com/research/surmount-5/

GLP Ranked. "SURMOUNT-5: Tirzepatide versus semaglutide, head to head." Updated 2026-07-24. https://glpranked.com/research/surmount-5/