SURMOUNT-1: how much weight tirzepatide took off in 72 weeks
At the top dose, people lost 20.9% of their body weight against 3.1% on placebo. Here is who was in the trial, what it cost them in side effects, and what it can’t tell you.
SURMOUNT-1 gave 2,539 adults with obesity weekly tirzepatide or placebo for 72 weeks. Average weight loss was 15.0% on 5 mg, 19.5% on 10 mg and 20.9% on 15 mg, against 3.1% on placebo [1]. Side effects were mostly gastrointestinal and front-loaded, and between 4% and 7% of people on the drug stopped because of them [1].
Why this study matters
Tirzepatide acts on two gut-hormone receptors, GIP and GLP-1, where semaglutide acts on one. SURMOUNT-1 tested it as an obesity treatment in people without diabetes at a point when its effects in that group were unknown [1], and it's one of the trials behind the FDA's approval of tirzepatide for chronic weight management as Zepbound in November 2023 [3].
The “20% weight loss” figure you'll see everywhere comes from this paper. It's real, but it belongs to the highest dose, and the paper reports it two different ways.
What they did
Everyone started on 2.5 mg, with the dose rising by 2.5 mg every four weeks until they reached their assigned dose, so the 15 mg group took 20 weeks to get there [1]. All groups had counselling aimed at a 500-calorie daily deficit and at least 150 minutes of activity a week.
The average participant was 44.9 years old, weighed 104.8 kg and had a BMI of 38.0. Two-thirds (67.5%) were women, 70.6% were White, and 40.6% had prediabetes [1]. Only 5.5% had a BMI in the 27 to 30 range [1], so this is really a trial of people with obesity, not overweight.
What they found
The main analysis counted every randomised participant, whether or not they kept taking their injections (the “treatment-regimen estimand”). A second analysis estimated what would happen if everyone took the drug as intended. Both are in the paper; the first is the more conservative [1].
| At week 72 | 5 mg | 10 mg | 15 mg | Placebo |
|---|---|---|---|---|
| Mean weight change (everyone randomised) | −15.0% | −19.5% | −20.9% | −3.1% |
| Mean weight change (if taken as intended) | −16.0% | −21.4% | −22.5% | −2.4% |
| Lost 5% or more | 85% | 89% | 91% | 35% |
| Lost 20% or more | not a key end point | 50% | 57% | 3% |
| Lost 25% or more (exploratory) | 15% | 32% | 36% | 1.5% |
Compared with placebo, the difference was 11.9, 16.4 and 17.8 percentage points for the three doses (p below 0.001 for each) [1]. In kilograms, the as-intended estimate at 15 mg works out to 23.6 kg [1].
Waist size, blood pressure, fasting insulin and lipids all improved more on tirzepatide [1]. Of the participants with prediabetes, 95.3% on tirzepatide had normal blood sugar at 72 weeks, against 61.9% on placebo [1].
A subgroup had DXA scans, and 160 of the 255 had usable scans at both ends of the trial. In them, fat mass fell 33.9% on tirzepatide against 8.2% on placebo, and the ratio of fat to lean mass dropped from 0.93 to 0.70 [1]. That suggests most of the weight lost was fat, though lean mass fell too and the subgroup is small.
Side effects
Between 78.9% and 81.8% of people on tirzepatide reported at least one adverse event, compared with 72.0% on placebo [1]. Nausea, diarrhoea and constipation led the list; the authors describe them as mostly mild to moderate and concentrated in the dose-escalation period.
Stopping because of side effects happened in 4.3%, 7.1% and 6.2% of the 5, 10 and 15 mg groups, and 2.6% on placebo [1]. Serious adverse events hit 6.3% of participants overall and were similar across groups, with roughly a fifth of them related to Covid-19, which ran through the trial period [1]. There were 11 deaths, spread across all four arms including four on placebo. Four adjudicated cases of pancreatitis were spread evenly across the groups, including placebo. Cholecystitis was more frequent on tirzepatide, but at 0.6% or less in any group [1].
Caveats
- Sponsor-run. Eli Lilly, which makes tirzepatide, designed the trial, monitored the sites and did the data analysis [1].
- Placebo dropouts. 86.0% of participants finished the 72 weeks, but completion was 88.4% to 89.8% on tirzepatide against 77.0% on placebo [1]. The statistical methods account for this, but it's a reminder that people who weren't losing weight tended to leave.
- Motivated volunteers with fairly healthy numbers. The authors note participants may have been more committed to weight management than most people with obesity, and that baseline blood pressure and lipids were relatively normal, which leaves less room to show improvement [1].
- No hard outcomes. Weight, waist and blood markers are not heart attacks, strokes or deaths. SURMOUNT-1 wasn't built to measure those.
The three-year follow-up
Participants who had prediabetes at the start (1,032 people) stayed on their assigned treatment for 176 weeks, a little over three years [2]. Weight loss held up: −12.3%, −18.7% and −19.7% on the three doses, against −1.3% on placebo. Type 2 diabetes was diagnosed in 1.3% of the tirzepatide groups and 13.3% of the placebo group (hazard ratio 0.07) [2]. After 17 weeks off treatment, those figures became 2.4% and 13.7%, so some of the protection started to fade once the drug stopped [2]. Lilly funded this analysis as well.
What it means in practice
In people with obesity and no diabetes, tirzepatide produced what its authors called an unusually large weight reduction compared with other phase 3 obesity trials, and at the higher doses about half of participants lost a fifth of their body weight [1]. The side-effect profile looks like the GLP-1 drugs: mostly gut symptoms, most of them early. Direct comparisons with semaglutide need a head-to-head trial, not two separate trials read side by side; different populations and methods make cross-trial comparisons unreliable.
What we still don’t know
- Whether the weight loss reduces heart attacks, strokes and deaths in people without diabetes; that needs an outcomes trial.
- What happens to weight after stopping over the longer term, since the 17-week off-drug window in the three-year analysis covered only people with prediabetes.
- How it performs in people with a BMI between 27 and 30, who were barely represented.
- The long-term effect on muscle and bone, given DXA data from 160 people.
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References
- [1]Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al.. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022. doi:10.1056/NEJMoa2206038
- [2]Jastreboff AM, le Roux CW, Stefanski A, Aronne LJ, Halpern B, Wharton S, et al.. Tirzepatide for obesity treatment and diabetes prevention. N Engl J Med 2025. doi:10.1056/NEJMoa2410819
- [3]US Food and Drug Administration. FDA approves new medication for chronic weight management (press release, 8 November 2023). FDA News Release 2023. www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management
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