Source of SURMOUNT trial programme

{{Infobox concept | name = SURMOUNT trial programme | subtitle = Phase 3 programme | image = trial-bars.svg | caption = Weight change by dose in the principal obesity trial. | Drug = [[Tirzepatide|Tirzepatide]] 5, 10 and 15 mg weekly | Indication = Chronic weight management | Principal duration = 72 weeks }} The '''SURMOUNT trial programme''' is the phase 3 series that established [[Tirzepatide|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.{{r|jastreboff2022}} 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]].{{r|jastreboff2022}} 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.{{r|garvey2023}} == Constituent trials == | 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]].{{r|garvey2023}} 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.{{r|jastreboff2022}} == Reading the figures == The 72-week duration includes a 20-week escalation, so as in [[STEP trial programme|STEP]] a substantial part of the trial was spent below the maintenance dose.{{r|jastreboff2022}} 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.{{r|garvey2023}} == Scope of the evidence == 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.{{r|ich_e9}} Nor does it establish comparative efficacy against [[Semaglutide|semaglutide]] 2.4 mg, which has never been studied head-to-head in obesity within this programme. Comparisons drawn between SURMOUNT-1 and [[STEP trial programme|STEP 1]] are cross-trial and are confounded by population, duration and escalation differences.{{r|ich_e9,wilding2021}} Means again conceal distribution: a substantial proportion of participants in every arm lost far more or far less than the mean, and the proportion achieving any given threshold is a more informative summary than the mean for a reader trying to understand the range of outcomes.{{r|jastreboff2022}} == References == {{reflist}} <ref name="jastreboff2022">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.</ref> <ref name="garvey2023">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.</ref> <ref name="ich_e9">International Council for Harmonisation, ''E9(R1): Estimands and Sensitivity Analysis in Clinical Trials'' (2019).</ref> <ref name="wilding2021">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.</ref> == External links == * [https://clinicaltrials.gov/study/NCT04184622 SURMOUNT-1 — NCT04184622] — Registry record for the pivotal obesity trial. == See also == * [[Tirzepatide]] * [[SURPASS trial programme]] * [[STEP trial programme]] * [[Weight regain after discontinuation]] * [[Placebo-adjusted effect]] {{DEFAULTSORT:SURMOUNT trial programme}} [[Category:Clinical trial programmes]] [[Category:Obesity trials]] [[Category:Clinical evidence]]