News · Clinical trials

SURMOUNT-5 Published: Tirzepatide 20.2% Against Semaglutide 13.7% in the First Head-to-Head

751 adults, 72 weeks, maximum tolerated doses of each — the only trial that has compared these two drugs directly for weight management.

Event date 2025-05-11 · Published 2026-07-24 · EV-0102

What was done

SURMOUNT-5 was a phase 3b, open-label, active-controlled trial at 32 sites across the United States and Puerto Rico, running from April 2023 to November 2024. It enrolled 751 adults with obesity — BMI 30 or above, or 27 or above with at least one obesity-related complication — and without type 2 diabetes, randomised 1:1.

Both arms titrated to maximum tolerated dose: tirzepatide 10 or 15 mg, semaglutide 1.7 or 2.4 mg, once weekly by subcutaneous injection for 72 weeks. The primary endpoint was percentage change in body weight at week 72. It was published in the New England Journal of Medicine in May 2025.

The results

Least-squares mean weight change was −20.2% with tirzepatide against −13.7% with semaglutide. In absolute terms −22.8 kg against −15.0 kg, a difference of about 7.8 kg. Waist circumference fell 18.4 cm against 13.0 cm. More participants on tirzepatide reached every threshold from 10% upward.

On safety: adverse events were predominantly gastrointestinal and mild to moderate in both arms. 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.

The three caveats that belong with it

Open-label. Neither participants nor investigators were blinded. For body weight measured on a scale that matters less than it would for a subjective endpoint, but unblinding can influence adherence and dropout.

Maximum tolerated dose, not fixed dose. The trial compared two titration strategies. That is arguably more clinically realistic and it makes the comparison less clean — and it is the caveat that the STEP UP readout for semaglutide 7.2 mg has since made more pointed.

Industry-funded. Eli Lilly funded a trial comparing its product against a competitor's. That does not make the result wrong — it is registered, peer-reviewed and published — but it belongs in the citation.

Why this trial anchors the whole category

Before it, the comparison was made by placing separate placebo-controlled trials side by side, which is a weak method: trials differ in eligibility, background support, geography, missing-data handling and estimand.

SURMOUNT-5 removed that problem, and its figures underpin most of the pricing logic in this market. Tirzepatide is priced above semaglutide almost universally, and this result is the justification.

What it does not establish

Anything about compounded preparations, microdoses or oral formulations. Both arms used FDA-approved subcutaneous injections at studied doses. Trial results do not transfer to a preparation that has not been through them, and this figure is quoted for compounded products constantly.

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