Design paper describes SURMOUNT-MMO, a 15,374-person tirzepatide outcomes trial

The design of SURMOUNT-MMO, a tirzepatide trial in adults with obesity who do not have diabetes, has been published in the journal Obesity ^[1]. The paper describes a 15,374-participant, event-driven study at 664 sites in 27 countries, with a five-component primary endpoint that includes all-cause death ^[1]. The authors describe it as the first incretin outcome trial to enroll people who have not yet developed cardiovascular disease ^[1].

Tirzepatide is the active ingredient in Mounjaro and Zepbound. The trial is listed on the U.S. National Library of Medicine's ClinicalTrials.gov as NCT05556512, under the title "A Study of Tirzepatide (LY3298176) on the Reduction on Morbidity and Mortality in Adults With Obesity" ^[2].

Participants are adults with obesity but without diabetes ^[1]. That makes the study a test of primary prevention: whether treatment reduces the chance of a first serious health event in people who have not yet developed cardiovascular disease ^[1]. The design paper frames SURMOUNT-MMO as the first incretin outcome trial to take that approach ^[1].

The primary endpoint combines five components, and all-cause death is one of them ^[1]. All-cause mortality means deaths from any cause during a study ^[2]. The trial is event-driven, meaning it is built around the number of health events that occur rather than a set calendar deadline ^[1].

The design paper's author list includes researchers from Eli Lilly and Company, the Cleveland Clinic Coordinating Center for Clinical Research, and academic centers in the United States, Europe and Asia ^[1]. Results have not been reported, and a date for reporting them has not been disclosed.

Why it matters for patients

For adults who have obesity but have not developed diabetes or cardiovascular disease, SURMOUNT-MMO is the first incretin outcome trial designed around them ^[1]. Findings would speak to whether tirzepatide lowers the risk of a first serious event, rather than whether it helps people who are already ill ^[1].

The primary endpoint includes all-cause death, a measure that counts deaths from any cause during the study ^[1][2]. Whether tirzepatide reduces deaths or serious illness in this group is not yet known. The trial has not reported results, so any claim that it does would be ahead of the evidence.

Outcome trials of this kind take years to finish because they wait for enough events to accumulate ^[1]. That means people deciding about treatment now will be making those decisions before this trial's answers exist.

What happens next

The publication puts the trial's design on the record ^[1]. No results and no reporting date have been disclosed. A companion commentary in the same issue of Obesity is titled "From Weight Loss to Multimorbidity Prevention: Framing the Anticipated Contributions of SURMOUNT-MMO," and discusses what the trial is expected to add ^[1].

The registry listing for NCT05556512 identifies the study as a tirzepatide trial measuring morbidity and mortality in adults with obesity ^[2]. Beyond that, details such as the tirzepatide dose used, the other four components of the primary endpoint, and enrollment status are not established in the published design paper described here.