Weight & Metabolic Health

SURMOUNT-MMO: the trial that decides whether tirzepatide gets a heart indication for people without diabetes

By the US Health Digest editorial team · Published September 4, 2026 · Every claim linked to its primary source

SURMOUNT-MMO is the phase 3 trial that will decide whether tirzepatide can claim a cardiovascular benefit in adults who do not have diabetes. Its ClinicalTrials.gov record (NCT05556512, last update posted January 12, 2026) lists 15,374 adults aged 40 and over with a BMI of at least 27.0, randomised to tirzepatide or placebo, with type 1 and type 2 diabetes among the exclusions. Estimated primary completion is October 2027. No results were published as of September 4, 2026.

This page reports what a trial registry, a design paper and current FDA labelling say. It is not advice to start, stop or change any medicine, and it does not predict what the trial will find.

Why this trial exists, and what the August 2026 approval left open

On August 28, 2026 the FDA approved Mounjaro (tirzepatide) to lower the risk of major adverse cardiovascular events — but only in adults with type 2 diabetes, on the strength of SURPASS-CVOT, which we covered in Mounjaro's new cardiovascular indication. The wording is now on the label: the DailyMed Mounjaro Structured Product Label, version 40, published September 2, 2026 and effective August 27, 2026, adds a second indication bullet: “to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction (MI), or non-fatal stroke) in adults with type 2 diabetes mellitus who are at high risk for these events.”

The Zepbound label — same molecule, same manufacturer, the product licensed for weight management — was republished the same day, also as version 40, effective August 28, 2026, and carries no cardiovascular indication: only weight reduction and obstructive sleep apnea. We read both SPLs rather than the press release alone, because a label question can only be settled by the label.

So the question left standing is the one most people taking tirzepatide for weight are actually asking: does it reduce cardiovascular events in someone without type 2 diabetes? SURMOUNT-MMO is the trial designed to answer it.

What the ClinicalTrials.gov record says, precisely

The registry entry is NCT05556512, sponsored by Eli Lilly and Company: “A Phase 3, Randomized, Double-blind, Placebo-Controlled Study to Investigate the Effect of Tirzepatide on the Reduction of Morbidity and Mortality in Adults With Obesity.” Key fields, retrieved September 4, 2026:

• Enrolment: 15,374, recorded as an actual count, not an estimate.
• Design: randomised, parallel, double-blind, tirzepatide escalated to a maximum tolerated dose versus matching placebo.
• Status: active, not recruiting. Actual start date October 11, 2022.
• Estimated primary completion: October 2027. Estimated study completion: also October 2027.
• Last update posted: January 12, 2026 (submitted January 9, 2026; status verified January 2026). Anything that has happened since then is not reflected in the record.

Who is in it — and who is explicitly kept out

The inclusion criteria require a “body mass index (BMI) ≥27.0 kilogram/square meter,” then split the population two ways. One route is “individuals ≥40 years of age with established cardiovascular disease (CVD),” defined as coronary artery disease, cerebrovascular disease or peripheral arterial disease. The other is primary prevention: “women 55-69 years of age or men 50-64 years of age with at least 3 risk factors like tobacco use, dyslipidemia, hypertension at screening,” or “women ≥70 years of age or men, ≥65 years of age with at least 2 risk factors at screening.”

The exclusions do the defining work. The list opens with “Have type 1 diabetes (T1D) or (T2D), history of ketoacidosis, or hyperosmolar state/coma,” then adds “laboratory evidence diagnostic of diabetes mellitus at screening of HbA1c ≥6.5% … or fasting glucose (FG) ≥126 milligram/deciliter.” An MI, acute coronary syndrome, stroke, revascularisation or decompensated heart failure within 90 days of screening also excludes. This is, by construction, a trial in people without diabetes.

The primary endpoint, in the registry's own words

The single primary outcome measure is titled “Time to First Occurrence of Any Component Event of Composite (All-Cause Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, Coronary Revascularization, or Heart Failure Events),” with the description “Time to first occurrence of any component event of composite, all-cause death, nonfatal MI, nonfatal stroke, coronary revascularization, or heart failure events that results in hospitalization or urgent visits.” Time frame: up to 5 years.

The design paper: PMID 40545827

The rationale and design were published as Lam CSP, Rodriguez A, Aminian A, et al. in Obesity (Silver Spring) 2025;33(9):1645–1656 (PMID 40545827, online June 22, 2025). We verified the PMID through NCBI's esummary service and read the structured abstract; we have not read the full paper or the protocol.

The abstract describes “a randomized, double-blind, event-driven trial to investigate the impact on morbidity and mortality with once-weekly tirzepatide compared with placebo in adults living with obesity, without diabetes, and with, or at risk of, cardiovascular disease.” The plan was to “enroll ~15,000 participants aged ≥40 from 664 sites across 27 countries”; the registry's as-run figures are 15,374 participants and 671 facility records across 28 country entries. Where the two documents differ, the registry is the later record.

One line from the conclusion is the trial's structural claim: “This is the first outcome trial of an incretin medication that assesses both primary and secondary cardiovascular disease prevention.” That is what separates it from the two trials below.

Have results been published? No — and here is what we searched

This is an absence claim, so it gets stated with its method. On September 4, 2026 we checked three independent places:

1. PubMed, via NCBI eutils. A search for SURMOUNT-MMO returned 8 records; we pulled the summary for each. They are the design paper, a same-issue commentary (“From Weight Loss to Multimorbidity Prevention: Framing the Anticipated Contributions of SURMOUNT-MMO”, PMID 40739460), reviews, a risk-modelling paper and an interview. None reports trial outcomes. A search on NCT05556512 returned one record, an unrelated 2026 hypertension review.
2. The ClinicalTrials.gov record itself. The API v2 response for NCT05556512 carries hasResults: false and contains no results section at all.
3. Eli Lilly's investor releases. We fetched Lilly's August 28, 2026 release announcing the Mounjaro cardiovascular approval and searched it: the string “SURMOUNT-MMO” does not appear, and it gives no timing guidance for further cardiovascular data. Web searches restricted to lilly.com and investor.lilly.com surfaced no release reporting SURMOUNT-MMO results or announcing a readout date.

On the sources we checked we found no published date for when results will be reported, and no date has been published for any FDA decision. The only forward-looking date on the public record is the registry's estimated primary completion of October 2027 — an estimate in an event-driven trial, which finishes when a target number of events has accrued, not on a calendar.

How SURMOUNT-MMO sits against the two trials that are finished

The SELECT and SURPASS-CVOT percentages come from their published abstracts (PMID 37952131, PMID 41406444), not press releases. Both are time-to-first-event analyses; SELECT's denominators are everyone randomised (8,803 and 8,801), while SURPASS-CVOT reports a modified intention-to-treat set after excluding 134 patients who did not meet inclusion criteria. Neither abstract names its estimand in those words, and SURMOUNT-MMO has no result to attach an estimand to yet — so these columns are not interchangeable.

The structural point is this. Semaglutide already has a cardiovascular indication in people without diabetes: the Wegovy label (SPL version 19, published June 30, 2026, effective June 18, 2026) lists as its first indication “to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV disease and either obesity or overweight.” Tirzepatide does not have that, and SURMOUNT-MMO is the trial that would have to supply the evidence for it. Note what Wegovy's indication still requires: established cardiovascular disease. SURMOUNT-MMO's second eligibility route — risk factors, no established disease — is territory neither drug has outcome evidence in.

What a five-component composite endpoint means when you read the result

SURMOUNT-MMO's primary endpoint counts the first occurrence of any of five things. SELECT and SURPASS-CVOT counted the first of three. That difference is worth understanding before the headline arrives rather than after.

More components means more events

An event-driven trial ends when a prespecified number of primary events has accrued. Widening the definition of “event” means events accumulate faster in both arms, so the trial reaches its target sooner and has more statistical power at a given size and duration. Counting all-cause death rather than cardiovascular death captures deaths from any cause, including cancer and infection. Counting coronary revascularisation captures a treatment decision — a stent or a bypass — which is more common than an infarction and depends partly on clinical practice. Heart failure events leading to hospitalisation or an urgent visit add a fourth disease process.

This is standard practice in outcome trials, particularly in primary-prevention populations where hard events are rarer. It is not a criticism. But it does mean that a positive five-component result and a positive three-component MACE result are not the same finding, and one does not automatically imply the other.

What to look at when the numbers land

The registry helps here, because it prespecifies the components separately. Its secondary outcome measures include “Time to First Occurrence of Any Component Event of Major Adverse Cardiovascular Events-3 (MACE-3) (CV Death, Nonfatal MI or Nonfatal Stroke),” plus individual measures for all-cause death, CV death, MI, stroke, coronary revascularisation and heart failure events — and, separately, time to onset of type 2 diabetes, change in eGFR, a kidney composite, body weight, blood pressure and an SF-36 physical functioning score. When results appear, the composite is the headline; the component breakdown and the MACE-3 secondary are what tell you which parts moved.

What this does and does not mean for you now

It does not change anything about any prescription today. No result exists. Nothing on this page is a reason to start, continue or stop a medicine, and no one can say which way the trial will go.

It does explain a gap you may have noticed. If you take tirzepatide for weight and read that Mounjaro now has a heart indication, that indication is not on your product and was not studied in people like you unless you have type 2 diabetes. That is a labelling fact, not a judgement about the drug.

It does mark where the evidence currently stops. For cardiovascular outcomes in people with obesity and no diabetes, the published randomised evidence is SELECT, it is semaglutide, and it required established cardiovascular disease. Our eligibility guide walks through what each current label actually says, our Wegovy versus Zepbound comparison sets the two products side by side, and the glossary defines MACE, composite endpoint and event-driven trial.

Questions for your prescriber

• Given my own history, am I in the group SELECT studied — established cardiovascular disease — or in the risk-factor group no completed outcome trial has covered?
• Is the indication on the specific product I am prescribed, or on a different brand of the same molecule?
• What is my cardiovascular risk being managed with now, independent of any weight medication?
• If SURMOUNT-MMO reports, what result would change your recommendation for me, and what would not?
• Would any of the registry's exclusion criteria — pancreatitis history, medullary thyroid carcinoma or MEN 2 family history, recent cardiac events — apply to me?

Frequently asked questions

What is SURMOUNT-MMO testing?

Whether once-weekly tirzepatide reduces morbidity and mortality compared with placebo in adults who have obesity or overweight but not diabetes. The ClinicalTrials.gov record NCT05556512 lists a single primary outcome: time to the first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularisation, or a heart failure event resulting in hospitalisation or an urgent visit, over up to 5 years. Enrolment is recorded as 15,374 actual participants, and the trial is listed as active, not recruiting.

When will SURMOUNT-MMO results be available?

No readout date has been published. The ClinicalTrials.gov record gives an estimated primary completion of October 2027 and an estimated study completion of October 2027, with the record last updated on January 12, 2026. Because the trial is event-driven, it concludes when a target number of events has accrued rather than on a fixed calendar date. We found no Eli Lilly release stating a readout date, and no date has been published for any FDA decision.

Does Zepbound have a cardiovascular indication?

No. The Zepbound Structured Product Label on DailyMed, version 40, published September 2, 2026 and effective August 28, 2026, is indicated to reduce excess body weight and maintain weight reduction long term in adults with obesity or overweight with at least one weight-related comorbid condition, and to treat moderate to severe obstructive sleep apnea in adults with obesity. It carries no cardiovascular indication. The August 2026 cardiovascular indication sits on the Mounjaro label and is limited to adults with type 2 diabetes at high risk for those events.

Why does semaglutide already have a heart indication for people without diabetes when tirzepatide does not?

Because SELECT has reported and SURMOUNT-MMO has not. SELECT enrolled 17,604 adults aged 45 or older with preexisting cardiovascular disease, a BMI of 27 or greater and no history of diabetes; a first three-component MACE event occurred in 6.5% on semaglutide 2.4 mg versus 8.0% on placebo, hazard ratio 0.80, 95% confidence interval 0.72 to 0.90. That result supports the Wegovy label's first indication, which is limited to adults with established cardiovascular disease and either obesity or overweight. Tirzepatide has no equivalent published outcome result outside type 2 diabetes.

Why does the number of endpoint components matter?

Because an event-driven trial ends when enough primary events have occurred, and a five-component endpoint accumulates events faster than a three-component one. Counting all-cause death rather than cardiovascular death, and counting coronary revascularisation and heart failure events alongside heart attack and stroke, gives more statistical power at the same trial size. That is a standard design choice, not a flaw, but it means a positive five-component result is not the same finding as a positive three-component MACE result. SURMOUNT-MMO prespecifies MACE-3 and each individual component as secondary outcome measures, so the breakdown should be readable when results appear.

Sources

1. ClinicalTrials.gov. SURMOUNT-MMO (NCT05556512). Phase 3, randomised, double-blind, placebo-controlled; actual enrolment 15,374; start October 11, 2022; active, not recruiting; estimated primary completion and estimated study completion October 2027; last update posted January 12, 2026. Record retrieved via API v2 on September 4, 2026; hasResults false.
2. Lam CSP, Rodriguez A, Aminian A, et al. Tirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of the SURMOUNT-MMO trial. Obesity (Silver Spring). 2025;33(9):1645–1656. PMID 40545827. Structured abstract read via NCBI eutils, September 4, 2026.
3. Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT). N Engl J Med. 2025;393(24):2409–2420. PMID 41406444. Registered as NCT04255433. Figures quoted from the PubMed structured abstract; the NEJM full text was not accessible to us.
4. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389(24):2221–2232. PMID 37952131. Registered as NCT03574597.
5. DailyMed. MOUNJARO (tirzepatide) injection. SPL version 40, published September 2, 2026; document effective August 27, 2026. Section 1.
6. DailyMed. ZEPBOUND (tirzepatide) injection. SPL version 40, published September 2, 2026; document effective August 28, 2026. Section 1.
7. DailyMed. WEGOVY (semaglutide) injection and tablets. SPL version 19, published June 30, 2026; document effective June 18, 2026. Section 1.
8. Eli Lilly and Company. FDA approves Lilly's Mounjaro (tirzepatide) to reduce cardiovascular risk, August 28, 2026. Searched September 4, 2026: contains no mention of SURMOUNT-MMO and no timing guidance for further cardiovascular data.