SURMOUNT trial programme (revision 19)
Old revision·03:47, 11 Jun 2025·StubSorterBot
| SURMOUNT trial programmePhase 3 programme | |
|---|---|
Weight change by dose in the principal obesity trial. | |
| Drug | Tirzepatide 5, 10 and 15 mg weekly |
| Indication | Chronic weight management |
| Principal duration | 72 weeks |
| Topic infobox · conventions | |
The SURMOUNT trial programme is the phase 3 series that established tirzepatide for chronic weight management. SURMOUNT-1 randomised 2,539 adults with obesity and without diabetes to tirzepatide 5, 10 or 15 mg weekly or placebo for 72 weeks.[1]
Mean weight change was −15.0%, −19.5% and −20.9% at the three doses against −3.1% on placebo. Both arms received lifestyle counselling, so the placebo figure is not a no-treatment baseline; see Placebo-adjusted effect.[1]
SURMOUNT-2 studied participants with obesity and type 2 diabetes and reported smaller reductions — −12.8% and −14.7% at 10 and 15 mg against −3.2% — reproducing the attenuation of weight response in diabetes seen across this field.[2]
Constituent trials
[edit]| Trial | Population | Duration | Result at highest dose |
|---|---|---|---|
| SURMOUNT-1 | Obesity, no diabetes | 72 weeks | −20.9% vs −3.1% |
| SURMOUNT-2 | Obesity with type 2 diabetes | 72 weeks | −14.7% vs −3.2% |
| SURMOUNT-3 | After intensive lifestyle lead-in | 72 weeks | Further loss after lead-in |
| SURMOUNT-4 | Randomised withdrawal after lead-in | 88 weeks total | Regain on withdrawal |
SURMOUNT-4 is the counterpart of STEP 4 and addresses the same question: what happens when treatment stops. Participants randomised to placebo after a lead-in regained a substantial proportion of the weight lost. See Weight regain after discontinuation.[2]
SURMOUNT-3 shows that a lifestyle lead-in does not exhaust the available effect: participants who had already lost weight on intensive lifestyle intervention lost further weight on active treatment.[1]
Reading the figures
[edit]The 72-week duration includes a 20-week escalation, so as in STEP a substantial part of the trial was spent below the maintenance dose.[1]
Weight-change curves at the higher doses were still declining at 72 weeks rather than plateauing, which limits what the endpoint figure says about the eventual effect and is one reason the programme's later trials run longer.
Discontinuation for adverse events ran at roughly 4–7% across doses, with gastrointestinal events dominating. That is comparable with agents producing smaller weight effects, which is one of the more interesting observations in the programme and is not fully explained.[2]
Scope of the evidence
[edit]The programme establishes weight efficacy in the studied populations and durations. It does not establish cardiovascular or other clinical outcomes; those are addressed by separate outcome trials, and weight is an intermediate endpoint.[3]
Nor does it establish comparative efficacy against semaglutide 2.4 mg, which has never been studied head-to-head in obesity within this programme. Comparisons drawn between SURMOUNT-1 and STEP 1 are cross-trial and are confounded by population, duration and escalation differences.[3][4]
See also
- Tirzepatide
- SURPASS trial programme
- STEP trial programme
- Weight regain after discontinuation
- Placebo-adjusted effect
References
- ^ a b c d Jastreboff AM, Aronne LJ, Ahmad NN, et al. "Tirzepatide once weekly for the treatment of obesity." New England Journal of Medicine 387(3):205–216 (2022). DOI:10.1056/NEJMoa2206038. PMID 35658024.
- ^ a b c Garvey WT, Frias JP, Jastreboff AM, et al. "Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2)." The Lancet 402(10402):613–626 (2023). PMID 37385275.
- ^ a b International Council for Harmonisation, E9(R1): Estimands and Sensitivity Analysis in Clinical Trials (2019).
- ^ Wilding JPH, Batterham RL, Calanna S, et al. "Once-weekly semaglutide in adults with overweight or obesity." New England Journal of Medicine 384(11):989–1002 (2021). PMID 33567185.