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SURMOUNT-1 · Jastreboff et al. · NEJM 2022

A 20.9% average drop at the highest dose — the largest seen in a GLP-1 trial.

How tirzepatide 15 mg performed across 72 weeks, and why it is studied alongside (not in place of) semaglutide.

SURMOUNT-1 was the pivotal randomized controlled trial for tirzepatide in chronic weight management. It enrolled 2,539 adults with obesity, or with overweight plus at least one weight-related complication, at 119 sites across 9 countries. Like STEP 1, it ran with a placebo arm and the same lifestyle counseling for everyone, double-blinded, over 72 weeks.

Tirzepatide is a "dual agonist" — it activates two receptors involved in appetite and glucose regulation (GIP and GLP-1), not just one. SURMOUNT-1 tested three doses: 5 mg, 10 mg, and 15 mg, all once weekly.

At week 72, average weight reductions were 15.0% with the 5 mg dose, 19.5% with 10 mg, and 20.9% with 15 mg. The placebo group lost 3.1% over the same window. The 20.9% figure that appears on the homepage refers to the 15 mg arm — the highest dose tested.

On secondary endpoints: 91% of participants on 15 mg lost at least 5% of body weight, and 57% lost at least 20%. As with semaglutide, the most common adverse events were gastrointestinal and concentrated during the early dose-escalation period.

Mean percent change in weight at week 72 was −15.0% with 5-mg weekly doses of tirzepatide, −19.5% with 10-mg doses, and −20.9% with 15-mg doses, as compared with −3.1% with placebo.
Jastreboff et al., New England Journal of Medicine, 2022

Plain-English read

Like STEP 1, this is a population-level number from a carefully run trial — not a guarantee about any one person. Tirzepatide is not "stronger semaglutide"; it works on a different combination of receptors, which is why side-effect profiles, dose schedules, and patient fit can differ. Your clinician will weigh whether tirzepatide is the right starting point for you, or whether semaglutide or a different protocol is a better match. Either way, the goal is the same: a plan you can actually stick with.

Peer-reviewed source

Tirzepatide Once Weekly for the Treatment of Obesity

Jastreboff AM, Aronne LJ, Ahmad NN, et al. · New England Journal of Medicine, 2022 · DOI: 10.1056/NEJMoa2206038

Read the full study on NEJM