SURMOUNT-1 Trial: Tirzepatide Weight Loss Results, Design, and How It Compares to STEP
SURMOUNT-1 established that once-weekly tirzepatide can produce substantial weight loss in adults with obesity or overweight without diabetes. At 72 weeks, average weight loss ranged from 15.0% to 20.9% across the three doses studied, compared with 3.1% with placebo. The trial helps explain what treatment can achieve over time; it does not set a required weight-loss target for every patient. [1]
What did SURMOUNT-1 study?
The randomized, double-blind trial assigned 2,539 adults to tirzepatide 5 mg, 10 mg, 15 mg, or placebo. Participants had a BMI of at least 30, or at least 27 with a weight-related complication. Diabetes was excluded. Treatment lasted 72 weeks, including a 20-week dose-escalation period. [1]
How much weight did participants lose?
The main results included participants regardless of whether they discontinued treatment. [1]
| Weekly treatment | Average weight loss at 72 weeks | Stopped treatment because of adverse events |
|---|---|---|
| Tirzepatide 5 mg | 15.0% | 4.3% |
| Tirzepatide 10 mg | 19.5% | 7.1% |
| Tirzepatide 15 mg | 20.9% | 6.2% |
| Placebo | 3.1% | 2.6% |
For perspective, 20% of a 250-pound starting weight is 50 pounds. That calculation translates a percentage into pounds; it is not a prediction for an individual. A useful treatment discussion considers changes in daily function and health goals alongside the scale.
Gastrointestinal symptoms were the most common adverse events, usually mild to moderate and concentrated during dose increases. [1]
How does SURMOUNT-1 compare with STEP 1?
STEP 1 studied semaglutide 2.4 mg weekly in 1,961 adults with overweight or obesity without diabetes. Average weight loss at 68 weeks was 14.9% with semaglutide versus 2.4% with placebo. Both groups received a lifestyle intervention. Gastrointestinal events led 4.5% of semaglutide participants and 0.8% of placebo participants to stop treatment. [2]
These are separate trials with different participants and follow-up schedules. Subtracting one trial's average from another does not measure the benefit of switching medicines. For a direct comparison, use SURMOUNT-5.
The direct comparison: SURMOUNT-5
SURMOUNT-5 randomized 751 adults with obesity without type 2 diabetes to the maximum tolerated weekly dose of tirzepatide, 10 or 15 mg, or semaglutide, 1.7 or 2.4 mg. At 72 weeks, average weight loss was 20.2% versus 13.7%, respectively. This open-label trial directly favored tirzepatide at the doses studied. [3]
Semaglutide 7.2 mg and oral semaglutide were not the comparison treatments. STEP UP separately tested weekly semaglutide 7.2 mg: average weight loss at 72 weeks was 18.7%, versus 15.6% with 2.4 mg and 3.9% with placebo. That study did not compare tirzepatide. [4]
What did the three-year SURMOUNT-1 follow-up show?
The longer analysis followed 1,032 participants who had both obesity and prediabetes at the start. At 176 weeks, average weight loss was 12.3%, 18.7%, and 19.7% with tirzepatide 5, 10, and 15 mg, respectively, versus 1.3% with placebo. [5]
Type 2 diabetes developed in 1.3% of tirzepatide participants versus 13.3% receiving placebo during treatment. After a further 17 weeks off treatment, those proportions were 2.4% and 13.7%. These findings concern the prediabetes subgroup, rather than everyone enrolled in the original trial. [5]
For someone with obesity and prediabetes, the study adds a concrete outcome to a weight-management discussion: progression to diabetes over three years. It does not mean follow-up glucose testing becomes unnecessary.
What happens when treatment stops?
SURMOUNT-4 addressed maintenance. After an initial 36 weeks of tirzepatide, 670 participants were randomized to continue it or switch to placebo for 52 weeks. Those continuing treatment lost another 5.5% of their week-36 weight on average; those switched to placebo gained 14.0%. [6]
The practical implication is to plan maintenance before starting. Discuss medication access, follow-up visits, and how the plan would change if treatment became unaffordable or difficult to tolerate. A temporary prescription and a long-term treatment plan are different commitments.
Applying the findings to a prescription
Zepbound contains tirzepatide and is approved for long-term weight management in eligible adults. Its starting dose is 2.5 mg weekly for four weeks. The maintenance doses for weight management are 5, 10, or 15 mg weekly, selected according to response and tolerability. The 15 mg trial result is not a reason to skip escalation or automatically pursue the highest dose. [7]
Bring three questions to follow-up:
- Is the current dose helping me reach the goals we set?
- Are symptoms interfering with eating, drinking, work, or daily activity?
- What is the plan for maintaining progress, including access to the next prescription?
Persistent severe abdominal pain, repeated vomiting, or inability to keep fluids down needs prompt medical attention. [7]
Common questions
Is SURMOUNT-1 a study of Zepbound or Mounjaro?
It is a study of tirzepatide for obesity. Zepbound is the tirzepatide brand with a weight-management indication. Use the prescribed product's instructions rather than treating a study dose as an interchangeable pen or vial instruction. [7]
Does everyone lose 20%?
No. A group average describes the study population. Your follow-up should assess your own trajectory, tolerability, and treatment goals.
Does this prove tirzepatide is the best option for everyone?
The trials answer specific questions about weight loss, maintenance, and diabetes progression. A prescription decision also needs the person's other health conditions, medication history, preferences, and reliable access to treatment.
References
- Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 2022.
- Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 2021.
- Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. New England Journal of Medicine, 2025.
- Wharton S et al. Once-weekly semaglutide 7.2 mg in adults with obesity: STEP UP. Lancet Diabetes & Endocrinology, 2025.
- Jastreboff AM et al. Tirzepatide for Obesity Treatment and Diabetes Prevention. New England Journal of Medicine, 2025.
- Aronne LJ et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction: SURMOUNT-4. JAMA, 2024.
- Eli Lilly. Zepbound U.S. prescribing information.