On August 28, 2026, the U.S. Food and Drug Administration approved a Mounjaro (tirzepatide) label expansion to reduce major adverse cardiovascular events in adults with type 2 diabetes who are at high risk for those events. The events on the indication are cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.
That is a Mounjaro indication in type 2 diabetes. It is not a Zepbound approval for obesity without diabetes, and it is not a finding that tirzepatide beat Trulicity.
The supporting trial is SURPASS-CVOT (NCT04255433), a head-to-head cardiovascular outcomes study against weekly dulaglutide 1.5 mg (Trulicity), not placebo. The New England Journal of Medicine paper reported that noninferiority was met and that superiority was not. Lilly's "8% lower rate" phrasing is 1 minus the published hazard ratio of 0.92. It is not a SELECT-style, placebo-controlled 20% result.
What happened
Eli Lilly announced the approval on August 28, 2026. The current U.S. Prescribing Information, revised August 2026, lists the new use under Indications and Usage and records "Major Adverse Cardiovascular Events (1) 08/2026" among Recent Major Changes. Section 14.6 now describes the cardiovascular outcomes trial.
Mounjaro was already approved, with diet and exercise, to improve glycemic control in adults and in pediatric patients 10 years of age and older with type 2 diabetes. The new cardiovascular claim applies to adults with type 2 diabetes at high risk for MACE. It does not extend the pediatric glycemic indication into a pediatric heart indication.
TIME's August 28 report independently confirmed the same event: FDA approved Mounjaro to lower the risk of heart events, including heart attack, in people with diabetes. TIME also recorded Lilly's point that the head-to-head design against Trulicity prevents a direct comparison with Novo Nordisk's Ozempic and Wegovy cardiovascular labels.
No separate FDA.gov news release for this supplement was located for this article. The independent primary anchors used here are the peer-reviewed SURPASS-CVOT publication, the ClinicalTrials.gov record, and the current FDA-approved U.S. label.
Why the trial design matters
Most incretin cardiovascular outcomes trials test a drug against placebo on top of standard care. SURPASS-CVOT did not. Investigators compared tirzepatide with dulaglutide, a GLP-1 receptor agonist that already has an FDA cardiovascular-risk-reduction indication in type 2 diabetes.
The NEJM paper describes an active-comparator, double-blind, noninferiority trial. Patients with type 2 diabetes and atherosclerotic cardiovascular disease were assigned 1:1 to weekly subcutaneous tirzepatide (up to 15 mg) or weekly dulaglutide 1.5 mg. The primary endpoint was a composite of death from cardiovascular causes, myocardial infarction, or stroke.
Noninferiority used a margin of 1.05 for the upper limit of the 95.3% confidence interval for the hazard ratio. An upper limit below 1.00 would have been treated as superiority. That is a high bar: the comparator already lowers cardiovascular risk versus placebo.
Lilly said it chose that bar on purpose. TIME quoted Rachel Batterham of Lilly saying the company compared Mounjaro with a drug that already reduced heart risk "to see if Mounjaro would have any additional benefit." The published statistics answer a narrower question. Tirzepatide was not worse than dulaglutide on MACE-3 by the pre-specified noninferiority rule. The trial did not show that it was better.
Evidence and study design
ClinicalTrials.gov NCT04255433 identifies SURPASS-CVOT as a completed Phase 3, randomized, double-blind, parallel-group trial sponsored by Eli Lilly. Actual enrollment was 13,299. The official title is "The Effect of Tirzepatide Versus Dulaglutide on Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes." Primary completion and completion are both listed as June 12, 2025.
| Item | Confirmed detail | Source |
|---|---|---|
| Trial | SURPASS-CVOT, NCT04255433 | ClinicalTrials.gov, NEJM, USPI |
| Population | Adults 40 and older with type 2 diabetes and established atherosclerotic cardiovascular disease | ClinicalTrials.gov, USPI |
| Glycemic and weight entry | HbA1c 7.0% to 10.5%; BMI at least 25 kg/m2 | ClinicalTrials.gov, USPI |
| Tirzepatide | Weekly, started at 2.5 mg, increased by 2.5 mg every 4 weeks, up to 15 mg or the maximum tolerated dose | ClinicalTrials.gov, USPI |
| Comparator | Weekly dulaglutide 1.5 mg (Trulicity), not placebo | NEJM, ClinicalTrials.gov, USPI |
| Primary endpoint | Time to first MACE-3 (cardiovascular death, MI, or stroke) | NEJM, USPI |
| Noninferiority rule | Upper 95.3% CI for the hazard ratio below 1.05 | NEJM |
| Follow-up | Median 210.1 weeks (about 4 years) | USPI, Lilly release |
| Sites | Lilly: 640 sites in 30 countries. ClinicalTrials.gov currently lists 635 locations across 31 countries. | Lilly release; ClinicalTrials.gov |
The NEJM paper is the peer-reviewed efficacy accounting. A total of 13,299 patients underwent randomization. Then 134 were excluded because they did not meet inclusion criteria. The modified intention-to-treat population was 6,586 on tirzepatide and 6,579 on dulaglutide.
Mean age was 64.1 years. Women were 29.0% of the cohort. Mean BMI was 32.6. Mean glycated hemoglobin was 8.4%. Mean diabetes duration was 14.7 years.
A primary endpoint event occurred in 801 of 6,586 patients (12.2%) on tirzepatide and 862 of 6,579 (13.1%) on dulaglutide. The hazard ratio was 0.92 (95.3% CI, 0.83 to 1.01). Noninferiority p was 0.003. Superiority p was 0.09. Superiority was not established.
The current U.S. label reports the same hazard ratio and the same 95.3% confidence interval, and it also states that superiority to dulaglutide was not established. Section 14.6 uses a slightly different analysis population: all randomized and treated participants, 6,647 in each arm. In that table, MACE-3 occurred in 803 patients (12.1%) on Mounjaro and 863 (13.0%) on dulaglutide. The label's noninferiority p-value for that analysis is 0.007.
Those two rows should not be mixed. The journal paper is the modified intention-to-treat result after the 134 post-randomization exclusions. The label table is the randomized-and-treated population. The hazard ratio is the same in both.
The label also reports all-cause death of 567 (8.5%) on Mounjaro and 670 (10.1%) on dulaglutide, hazard ratio 0.84 (95% CI, 0.75 to 0.94). That comparison is footnoted as not controlled for the family-wise type I error rate. It is a labeled secondary observation, not a multiplicity-controlled superiority win on death.
Adverse events appeared similar overall in the NEJM report, with more gastrointestinal events on tirzepatide. Lilly said the safety and tolerability of Mounjaro were generally consistent with its established profile, and that the most common SURPASS-CVOT adverse events on Mounjaro were gastrointestinal, generally mild to moderate, and mainly during dose escalation.
What the 8% figure is
Lilly's release says Mounjaro had an "8% lower rate" of cardiovascular death, heart attack, or stroke versus Trulicity. That is a restatement of 1 minus 0.92. TIME used the same 8% figure.
It is not a 20% placebo-controlled benefit. SELECT tested semaglutide 2.4 mg against placebo in people with overweight or obesity and established cardiovascular disease, without requiring diabetes. SURPASS-CVOT tested tirzepatide against an active GLP-1 drug that already has a cardiovascular indication. The populations, comparators, and statistical questions are different. Cross-trial percentage shopping is not a ranking.
PeptidePrices' tirzepatide research page currently describes SURPASS-CVOT as reporting roughly a 26% MACE reduction. That sentence conflicts with the published NEJM result and with the current U.S. label, both of which report a hazard ratio of 0.92. The research page needs a correction. This article does not rewrite that page.
What this does not mean
- It is not a Zepbound heart approval. The new indication is on Mounjaro, for adults with type 2 diabetes at high cardiovascular risk. Zepbound is a separate tirzepatide brand for chronic weight management and related uses. TIME quoted Lilly saying the company does not yet have the data to say the same heart benefit applies in people without diabetes.
- It is not superiority over Trulicity. Noninferiority was met. Superiority was not. An 8% relative difference with a confidence interval that crosses 1.00 is not a demonstrated win against dulaglutide.
- It is not comparable to SELECT, Ozempic, or Wegovy cardiovascular labels. Those programs used placebo controls and different populations. TIME made the same comparison warning.
- It is not a pediatric cardiovascular indication. The glycemic indication includes patients 10 years and older. The MACE indication is for adults.
- It is not evidence about compounded or research-vendor tirzepatide. The approved product is prescription Mounjaro. Compounded tirzepatide and research-chemical listings are not this FDA-approved drug product and were not the article tested in SURPASS-CVOT.
- It does not make tirzepatide a general heart drug for anyone with risk factors. SURPASS-CVOT enrolled people with type 2 diabetes and established atherosclerotic cardiovascular disease. The label language is adults with type 2 diabetes at high risk for MACE.
What to watch next
The open cardiovascular question is obesity without diabetes. SURMOUNT-MMO (NCT05556512) is Lilly's Phase 3, randomized, double-blind, placebo-controlled outcomes trial of tirzepatide in adults with obesity or overweight who do not have diabetes. ClinicalTrials.gov lists the study as active, not recruiting. Actual enrollment is 15,374. Estimated primary completion and completion are October 2027.
The registered primary endpoint is time to first event in a five-component composite: all-cause death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or heart-failure events leading to hospitalization or urgent visits. That is a broader endpoint than SURPASS-CVOT's MACE-3, and the comparator is placebo, not dulaglutide.
TIME reported Lilly's comment that the Zepbound heart-event study is looking at both first events and second events, and that those data were expected "next year." The public registry's October 2027 completion date is the dated record. A company quote in a news story is not the same thing as a completed trial.
Until SURMOUNT-MMO reads out, the August 28 decision should be described in its actual scope: a Mounjaro label in type 2 diabetes, supported by a noninferiority result against Trulicity.
For readers comparing incretin labels more broadly, see our earlier map of GLP-1 indications beyond weight loss and the ADA 2026 pipeline roundup. Live tirzepatide listing comparisons remain a price-and-vendor view, not a substitute for the approved drug label.
FAQs
Did FDA approve Mounjaro to lower heart-event risk?
Yes. On August 28, 2026, FDA approved Mounjaro to reduce MACE (cardiovascular death, non-fatal heart attack, or non-fatal stroke) in adults with type 2 diabetes at high risk for those events. The current U.S. label, revised August 2026, includes that indication.
Did Mounjaro beat Trulicity?
No. SURPASS-CVOT met noninferiority versus weekly dulaglutide 1.5 mg. In the NEJM modified intention-to-treat analysis, MACE-3 occurred in 12.2% on tirzepatide and 13.1% on dulaglutide (HR 0.92; 95.3% CI, 0.83 to 1.01; P=0.003 for noninferiority; P=0.09 for superiority). Superiority was not established.
Does this apply to Zepbound or to people without diabetes?
No. This is a Mounjaro type 2 diabetes indication. The obesity-without-diabetes outcomes trial is SURMOUNT-MMO (NCT05556512), which is still ongoing.
Can the 8% figure be compared with Wegovy's SELECT result?
No. The 8% figure is 1 minus 0.92 from an active-comparator trial against Trulicity. SELECT was a placebo-controlled trial in a different population. The numbers are not interchangeable.
Is compounded or research-vendor tirzepatide the same product?
No. The approval applies to prescription Mounjaro. Compounded products and research-use listings are not this FDA-approved product and were not the intervention in SURPASS-CVOT.
Where can the primary numbers be checked?
The NEJM paper, ClinicalTrials.gov NCT04255433, and section 14.6 of the current Mounjaro U.S. Prescribing Information. Lilly's August 28 release is the company event source, not a substitute for those records.
This article is for general informational purposes only and is not medical advice. Talk to a licensed clinician about personal medical decisions.
Continue your research
- Tirzepatide price comparison
- Tirzepatide research page
- GLP-1s Are Becoming "Everything" Drugs: The New Indications Beyond Weight Loss
- What the GLP-1 Pipeline Showed at ADA 2026
Sources
- Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med. 2025;393:2409-2420. DOI 10.1056/NEJMoa2505928
- ClinicalTrials.gov NCT04255433. SURPASS-CVOT
- Mounjaro (tirzepatide) U.S. Prescribing Information, revised August 2026. Indications and Usage; section 14.6
- Eli Lilly. FDA approves Lilly's Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes. PR Newswire. August 28, 2026
- Alice Park. Mounjaro Is Now Approved to Lower the Risk of Heart Events. TIME. August 28, 2026
- ClinicalTrials.gov NCT05556512. SURMOUNT-MMO