- In STEP 1, people on semaglutide 2.4 mg lost 14.9% of their body weight on average over 68 weeks, vs 2.4% on placebo.1
- In SURMOUNT-1, people on tirzepatide lost 15.0% to 20.9% over 72 weeks depending on dose, vs 3.1% on placebo.2
- Results vary a lot from person to person. An average of 15% means some people lost far more and some far less.
Why these two trials matter
STEP 1 is the trial that led to semaglutide 2.4 mg (sold as Wegovy) being approved for weight management. SURMOUNT-1 did the same for tirzepatide (sold as Zepbound). Both were large, randomized and placebo-controlled: people were assigned to the medicine or a placebo by chance, and neither they nor the researchers knew who got which. That design is the strongest evidence we have for what a medicine does.
In both trials, everyone, including the placebo group, also got lifestyle counselling: a reduced-calorie diet and more physical activity. So the placebo group shows roughly what diet and exercise support alone achieved in the same setting.
STEP 1: semaglutide 2.4 mg
STEP 1 enrolled 1,961 adults with a BMI of 30 or more, or 27 or more with at least one weight-related condition such as high blood pressure. People with diabetes were not included. Participants took a once-weekly injection for 68 weeks.1
Averages hide the spread, so the trial also reported how many people crossed certain thresholds:
| Lost at least | Semaglutide | Placebo |
|---|---|---|
| 5% of body weight | 86.4% | 31.5% |
| 10% | 69.1% | 12.0% |
| 15% | 50.5% | 4.9% |
| 20% | 32.0% | 1.7% |
Put simply: about half of the people on semaglutide lost 15% or more, and about a third lost 20% or more. For someone who starts at 100 kg (220 lb), 15% is 15 kg (33 lb).
SURMOUNT-1: tirzepatide
SURMOUNT-1 enrolled 2,539 adults with similar criteria and no diabetes. Participants took tirzepatide at 5 mg, 10 mg or 15 mg once a week, or placebo, for 72 weeks.2
At least 5% of body weight was lost by 85%, 89% and 91% of people on the three doses, vs 35% on placebo. At the two higher doses, about half or more lost at least 20%: 50% on 10 mg and 57% on 15 mg, vs 3% on placebo.2
Side effects: mostly the stomach, mostly early
The most common side effects in both trials were gastrointestinal: nausea, diarrhea, constipation and vomiting. In STEP 1, 74.2% of people on semaglutide reported a gastrointestinal side effect at some point, vs 47.9% on placebo. Most were mild to moderate and happened while the dose was being increased. 7.0% of people on semaglutide stopped the medicine because of side effects, vs 3.1% on placebo.1
That pattern, side effects clustered around the first weeks and each dose increase, is why many people find it useful to note how they feel in the days after each dose. It makes it easier to describe the pattern to your care team.
How to read these numbers for yourself
- They are averages from 68 to 72 weeks. In both trials, weight came down over many months and only levelled off towards the end. A slow month early on does not tell you much about where you will end up.
- Everyone also had diet and activity support. The trial results are medicine plus lifestyle changes, not medicine alone.
- Not all weight lost is fat. Some lean mass, which includes muscle, is lost too. That is why protein and strength training get so much attention. Read how much protein the research suggests.
- The results last while the medicine continues. Trials where people stopped show substantial regain. See what happened when people stopped.
- Different medicines and doses are not interchangeable. These trials compared each medicine with placebo, not with each other. Your care team chooses a medicine and dose for you.
Sources
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384:989-1002. NEJM · PubMed
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387:205-216. NEJM · PubMed
