The short answer
Yes, in SURMOUNT-3. People who had already lost at least 5% of their weight during an intensive lifestyle program lost substantially more after being assigned tirzepatide. The important detail: the randomized trial began only after that initial success.
A head start before randomization
The study enrolled 806 adults with obesity, or overweight plus a weight-related complication, without diabetes. Everyone first took part in a 12-week intensive lifestyle program.
Of those enrolled, 579 met the weight-loss target and other criteria needed to enter the randomized phase. They had lost an average of 6.9% of their starting weight. They were then assigned either weekly tirzepatide at their maximum tolerated study dose of 10 or 15 mg, or placebo, for another 72 weeks.
This design asks whether medicine can build on successful lifestyle changes. It does not ask whether people have to “fail” a lifestyle program before medication can help.
Percentage of weight at randomization
Original chart based on the study. Values are reported group averages.
| Group | Average weight change |
|---|---|
| Tirzepatide | −18.4% |
| Placebo | +2.5% |
What happened next
From the start of the randomized phase, average weight changed by −18.4% with tirzepatide and +2.5% with placebo. The analysis included participants regardless of whether they stayed on their assigned treatment.
These percentages start from the participants' weight after the lifestyle program. They are not percentages of the original screening weight. Adding 6.9 and 18.4 directly would mix two different starting points.
About 87.5% assigned tirzepatide achieved at least another 5% reduction, compared with 16.5% assigned placebo. The results support an additional effect in people who had already responded to the lifestyle program.
The trade-off was tolerability
Digestive symptoms were the most common side effects, generally mild or moderate. Nausea occurred in 39.7% of the tirzepatide group and 14.0% of the placebo group.
Adverse events led 10.5% of tirzepatide participants to stop treatment, compared with 2.1% receiving placebo. A substantial average benefit and difficulty tolerating treatment can both be true; the discontinuation result is part of the story.
Who was left out of this comparison?
People who did not lose at least 5% during the initial program were not randomized. That selection makes the result particularly useful for understanding what happened after successful lifestyle weight loss, but less direct for people who did not respond to that program.
The study population was also predominantly White and recruited in North and South America. It did not compare tirzepatide against semaglutide or another active weight-loss medicine.
The practical takeaway: Lifestyle progress and medication benefit are not mutually exclusive. This trial tested them in sequence and found additional average weight loss with tirzepatide. It does not establish one required sequence for everyone.
Sources
Wadden TA and colleagues. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nature Medicine, 2023, corrected publication 2024. Full paper · DOI. Funded by Eli Lilly.