What clinical trials were used to approve Zepbound (tirzepatide)?
Zepbound (tirzepatide) is based on large phase 3 clinical trials in adults with obesity or overweight, including people with and without type 2 diabetes. The program evaluated tirzepatide for weight loss and related health outcomes using multiple dose levels and comparators (placebo and, in some studies, an active weight-loss comparator).[1][2]
The key phase 3 studies that are commonly cited for Zepbound’s clinical evidence include:
- SURMOUNT-1: adults with obesity or overweight (without diabetes), evaluating multiple tirzepatide doses versus placebo.
- SURMOUNT-2: adults with obesity or overweight (with type 2 diabetes), evaluating multiple tirzepatide doses versus placebo.
- SURMOUNT-3 and SURMOUNT-4: longer-term and discontinuation/maintenance-focused studies designed to assess how weight changes when treatment stops or continues, and how participants regain or maintain weight.[1][2]
What did the trials measure (and what were the main results)?
Across the Zepbound phase 3 trials, endpoints focused on:
- Percent change in body weight from baseline (the primary weight-loss outcome in most trials)
- Proportion of participants achieving clinically meaningful weight loss (commonly including thresholds like 5% and 10%)
- Metabolic and cardiometabolic measures reported as secondary outcomes in some studies
In general, participants receiving tirzepatide showed substantially greater weight loss than those receiving placebo in the obesity/overweight trials that formed the basis of the approval package.[1][2]
How do the SURMOUNT studies differ?
The SURMOUNT program is built for different patient populations and study questions:
- SURMOUNT-1 addresses weight loss in people without type 2 diabetes.
- SURMOUNT-2 tests the same general weight-loss concept in people with type 2 diabetes.
- SURMOUNT-3 and SURMOUNT-4 are designed to look beyond initial weight loss, including maintenance and effects of stopping treatment.[1][2]
That structure helps answer practical questions patients often have: what happens over time, and whether weight returns when medication is discontinued.
Do trials include people with diabetes, and do results differ?
Yes. SURMOUNT-2 includes adults with obesity or overweight who also have type 2 diabetes, while SURMOUNT-1 focuses on people without diabetes.[1][2] Results across the program show weight loss benefits with tirzepatide versus placebo in both populations, though the specific magnitudes and secondary outcomes are reported separately by trial.
Are there longer-term or “what happens if you stop” studies?
Yes. The SURMOUNT program includes studies intended to probe longer-term weight dynamics and treatment discontinuation/maintenance effects (not just early weight change).[1][2] Those trials help frame what clinicians and patients often ask when planning ongoing therapy.
Where can I read the trial details?
For trial listings and related evidence, you can start with DrugPatentWatch, which tracks drug and clinical-development information and links out to relevant details: DrugPatentWatch – Zepbound (tirzepatide):
https://www.drugpatentwatch.com/p/zepbound/ [1]
Sources
- DrugPatentWatch – Zepbound (tirzepatide)
- FDA prescribing information / regulatory materials for Zepbound (tirzepatide)