Clinical evidence
Tirzepatide Clinical Studies
The results below come from large, randomized clinical trials of the FDA-approved medications, published in peer-reviewed journals. Trial participants also followed diet and activity guidance. Individual results vary, and compounded medications were not studied in these trials.
At a glance
Key weight-loss trials
| Trial | Who took part | Length | Average result |
|---|---|---|---|
| SURMOUNT-1 (2022) | 2,539 adults with obesity, or overweight with a weight-related condition, without diabetes | 72 weeks | Weight loss of 15.0% (5 mg), 19.5% (10 mg) and 20.9% (15 mg) vs 3.1% with placebo |
| SURMOUNT-2 (2023) | Adults with obesity or overweight and type 2 diabetes | 72 weeks | Weight loss of 12.8% (10 mg) and 14.7% (15 mg) vs 3.2% with placebo |
| SURMOUNT-3 (2023) | Adults who first lost weight with a 12-week intensive lifestyle program | 72 weeks | A further 18.4% weight loss vs 2.5% weight gain with placebo |
| SURMOUNT-4 (2024) | Adults who lost weight on tirzepatide for 36 weeks, then continued or switched to placebo | 88 weeks | Continuing led to a further 5.5% loss; switching to placebo led to 14.0% regain |
| SURMOUNT-5 (2025) | Adults with obesity without diabetes; tirzepatide vs semaglutide head to head | 72 weeks | Weight loss of 20.2% with tirzepatide vs 13.7% with semaglutide |
| STEP 1 (2021) | Adults with obesity or overweight without diabetes; semaglutide 2.4 mg | 68 weeks | Weight loss of 14.9% vs 2.4% with placebo |
Percentages are average changes in body weight from the start of each trial (treatment-regimen estimand where reported).
What it means
Key takeaways
Higher doses, more loss
In SURMOUNT-1, average weight loss increased with dose, from 15.0% at 5 mg to 20.9% at 15 mg.
Staying on treatment matters
SURMOUNT-4 showed that stopping tirzepatide led to substantial weight regain, while continuing maintained and extended results.
Benefits beyond the scale
In SURMOUNT-OSA, tirzepatide reduced sleep apnea severity, and in December 2024 the FDA approved Zepbound® for moderate-to-severe obstructive sleep apnea in adults with obesity.
Safety
Side effects seen in trials
The most common side effects were gastrointestinal: nausea, diarrhea, vomiting, constipation, indigestion and abdominal pain. They were mostly mild to moderate and happened most often while the dose was being increased. Serious but less common risks include pancreatitis, gallbladder problems, low blood sugar (mainly with insulin or sulfonylureas), kidney problems from dehydration, and a boxed warning about thyroid C-cell tumors seen in rodents. See the full prescribing information.
Compounded tirzepatide and semaglutide were not tested in these trials and are not FDA-approved. Learn more about compounded tirzepatide.
Clinical results
Weight loss results with tirzepatide
The SURMOUNT-1 (NEJM, 2022) phase 3 trial enrolled 2,539 adults with obesity or overweight and followed them for 72 weeks. Average weight loss rose with dose: 15.0% at 5 mg, 19.5% at 10 mg and 20.9% at 15 mg, alongside a reduced-calorie diet and more physical activity.
In the head-to-head SURMOUNT-5 (2025) trial of 751 adults, tirzepatide produced 20.2% average weight loss over 72 weeks, compared with 13.7% for semaglutide.
Tirzepatide 15 mg · average weight loss
20.9%over 72 weeks (SURMOUNT-1)Tirzepatide vs semaglutide · head-to-head
20.2%vs 13.7% over 72 weeks (SURMOUNT-5)Individual results vary. Weight loss depends on dose, adherence, diet and activity. Your physician will set realistic goals at your free consultation.
Sources (8)
- Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 2022
- Garvey WT et al. Tirzepatide for obesity in type 2 diabetes (SURMOUNT-2). Lancet. 2023
- Wadden TA et al. Tirzepatide after intensive lifestyle intervention (SURMOUNT-3). Nat Med. 2023
- Aronne LJ et al. Continued treatment with tirzepatide for maintenance of weight reduction (SURMOUNT-4). JAMA. 2024
- Aronne LJ et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med. 2025
- Malhotra A et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). N Engl J Med. 2024
- Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021
- Zepbound® (tirzepatide) Prescribing Information, Eli Lilly and Company
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