Tirzepatide Once Weekly for Obesity: Results from the SURMOUNT-1 Trial | Research

The takeaway

Weekly tirzepatide injections helped people with obesity lose up to 21% of their body weight over 72 weeks — far more than placebo.

20.9% weight loss
Mean body weight reduction at 72 weeks with tirzepatide 15 mg, compared to 3.1% with placebo

What the researchers found

Tirzepatide, a dual GIP/GLP-1 receptor agonist, produced dose-dependent weight loss that far exceeded placebo in adults with obesity but without diabetes. At week 72, mean weight loss was 15.0% with 5 mg, 19.5% with 10 mg, and 20.9% with 15 mg, compared to just 3.1% with placebo (P<0.001 for all comparisons).

At the highest dose, 91% of participants lost at least 5% of their body weight and 57% lost at least 20% — a threshold previously achievable mainly through bariatric surgery. Improvements were observed across all prespecified cardiometabolic measures. Gastrointestinal side effects were the most common but were predominantly mild to moderate and occurred primarily during the 20-week dose-escalation period.

Why it matters

This trial established tirzepatide as one of the most effective anti-obesity medications ever tested, producing weight loss approaching what was previously only seen with surgery. As the pivotal trial supporting Zepbound's FDA approval for obesity, SURMOUNT-1 reshaped expectations for what pharmacotherapy can achieve in weight management and opened the door for a new class of dual-agonist peptide drugs.

How the study worked

This was the SURMOUNT-1 trial — a phase 3, double-blind, randomized, placebo-controlled study. A total of 2,539 adults with a BMI of 30 or higher (or 27+ with at least one weight-related complication), excluding those with diabetes, were randomly assigned 1:1:1:1 to receive subcutaneous tirzepatide at 5 mg, 10 mg, or 15 mg, or placebo, once weekly for 72 weeks. Doses were gradually escalated over the first 20 weeks. The two primary endpoints were percentage change in body weight and the proportion achieving at least 5% weight loss.

What this study cannot tell us

The trial excluded people with diabetes, so results may not directly apply to that population (separate trials addressed this). The 72-week duration, while substantial, does not answer questions about weight maintenance after stopping the drug. The study population was predominantly female and had a mean BMI of 38, so results may vary in other demographics. Gastrointestinal side effects led to discontinuation in up to 7.1% of participants at the 10 mg dose.

How to read the evidence

This is among the highest quality of clinical evidence: a large (n=2,539), phase 3, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine. The study used intention-to-treat analysis and had clearly defined primary endpoints with highly statistically significant results.

When this study was published

Published in 2022, this is the pivotal SURMOUNT-1 trial that supported FDA approval of tirzepatide (Zepbound) for obesity. It remains the foundational reference for tirzepatide in weight management.

The bigger picture

SURMOUNT-1 was a landmark moment for obesity pharmacotherapy. Before tirzepatide, the most effective approved weight-loss drug (semaglutide 2.4 mg) produced about 15% weight loss. Tirzepatide's dual GIP/GLP-1 mechanism pushed that ceiling to over 20%, entering territory once reserved for bariatric surgery. This trial helped establish the principle that targeting multiple incretin pathways simultaneously can amplify metabolic benefits, influencing the entire pipeline of next-generation obesity drugs.

Questions still open

How much weight do patients regain after stopping tirzepatide, and can maintenance strategies prevent this?
Does tirzepatide's dual GIP/GLP-1 mechanism preserve more lean muscle mass compared to GLP-1-only drugs during weight loss?
What are the cardiovascular outcomes with long-term tirzepatide use in people with obesity?

Common questions

How much weight can you lose on tirzepatide for obesity?

In this trial, participants lost an average of 15% to 21% of their body weight depending on the dose, over 72 weeks. At the highest dose (15 mg), more than half of participants lost at least 20% of their body weight — comparable to outcomes sometimes seen with bariatric surgery.

What are the most common side effects of tirzepatide?

The most common side effects were gastrointestinal — including nausea, diarrhea, and constipation. Most were mild to moderate and occurred mainly during the first 20 weeks as the dose was gradually increased. Between 4% and 7% of participants stopped treatment due to side effects, depending on the dose.

Read the original research

Tirzepatide Once Weekly for the Treatment of Obesity.

The New England journal of medicine, 387(3), 205-216

View on PubMed ↗Publisher’s paper ↗

Citation

Jastreboff, Ania M; Aronne, Louis J; Ahmad, Nadia N; Wharton, Sean; Connery, Lisa; Alves, Breno; Kiyosue, Arihiro; Zhang, Shuyu; Liu, Bing; Bunck, Mathijs C; Stefanski, Adam. (2022). Tirzepatide Once Weekly for the Treatment of Obesity.. The New England journal of medicine, 387(3), 205-216. https://doi.org/10.1056/NEJMoa2206038