FDA Approves Mounjaro to Lower Cardiovascular Risk in Type 2 Diabetes Based on SURPASS-CVOT

The FDA approved tirzepatide (Mounjaro) to lower the risk of major adverse cardiovascular events (MACE) — cardiovascular death, non-fatal heart attack, or non-fatal stroke — in adults with type 2 diabetes who are at high risk for these events.¹ Mounjaro, a dual GIP and GLP-1 receptor agonist, was already approved as an adjunct to diet and exercise to improve blood sugar in adults and children 10 and older with type 2 diabetes; this approval adds a cardiovascular risk-reduction indication on top of its established glycemic and weight-loss benefits.¹ Lilly describes Mounjaro as the first and only GIP/GLP-1 receptor agonist proven to lower this risk.¹

What did the trial show?

The approval is based on SURPASS-CVOT, described by Lilly as the first cardiovascular outcomes trial to compare two incretin medicines head-to-head rather than against placebo, and the largest and longest tirzepatide study to date, enrolling more than 13,000 participants across 30 countries over more than four and a half years.¹ Mounjaro demonstrated non-inferiority to Trulicity (dulaglutide), a GLP-1 therapy with established cardiovascular benefit, with an 8% lower rate of cardiovascular death, heart attack, or stroke.¹ The estimated hazard ratio for time to first MACE was 0.92 (95.3% CI: 0.83, 1.01).¹ Full results were published in the New England Journal of Medicine: over a median follow-up of four years, the primary composite endpoint occurred in 12.2% of tirzepatide-treated patients versus 13.1% of dulaglutide-treated patients, meeting statistical criteria for non-inferiority (P = 0.003) but not superiority (P = 0.09).² Dulaglutide was selected as the active comparator rather than placebo because of prior evidence, including the REWIND trial, establishing its own cardiovascular benefit in this population, making it considered unethical to randomize high-risk patients to placebo alone.²

"Heart health deserves attention throughout the course of treatment, not just after a serious cardiovascular event," said David A. D'Alessio, MD, study co-author and director of the Division of Endocrinology and Metabolism at Duke University School of Medicine. "While a large portion of type 2 diabetes care is focused on glucose control, mitigating cardiovascular risk is essential and can be overlooked. This approval gives patients a medicine that reduces the risk of cardiovascular events and supports metabolic health at the same time."¹

Why does this matter for patients with type 2 diabetes?

Lilly states that as many as one in three adults in the US with type 2 diabetes have undetected cardiovascular disease.¹ This is broadly consistent with independent findings from the multinational CAPTURE study, which found approximately one in three adults with type 2 diabetes had diagnosed cardiovascular disease as of 2019 — a related but distinct measure from Lilly's claim about undetected disease, since CAPTURE assessed diagnosed rather than silent cardiovascular disease. CAPTURE separately found that use of glucose-lowering therapies with demonstrated cardiovascular benefit remained low even among patients with established disease.³ Heart disease remains the leading cause of death for people with type 2 diabetes.¹

"For people with type 2 diabetes, heart disease is the leading cause of death, and Mounjaro – the #1 most prescribed branded type 2 diabetes medicine for adults in the U.S. – now gives them a proven way to lower that risk, adding to the strong foundation it has already built in A1C and weight," said Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health. "We set a higher bar by testing Mounjaro against a GLP-1 medicine with proven cardiovascular benefit, one that reflects the depth of evidence Lilly continues to build in this field."¹

What does this mean for Mounjaro's broader trajectory?

Mounjaro first reached the market in May 2022 as a type 2 diabetes treatment before expanding into obesity and sleep apnea indications under the Zepbound brand name; BioPharm International^© has covered tirzepatide's rapid expansion across the incretin drug class since then.⁴ This cardiovascular indication extends tirzepatide's label further, building on data already incorporated into Mounjaro's product information in the European Union, with regulatory submissions based on SURPASS-CVOT under review in additional markets.¹

What's next?

The safety and tolerability profile observed in SURPASS-CVOT was generally consistent with Mounjaro's established profile, with gastrointestinal-related adverse events remaining the most common, mild-to-moderate in severity, and concentrated during the dose-escalation period.¹ Regulatory review of the SURPASS-CVOT data continues in markets beyond the EU and US.¹

References

1. FDA approves Lilly's Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes. News release. Eli Lilly and Company; August 28, 2026. Accessed August 28, 2026.
2. Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med. 2025;393(24):2409-2420. doi:10.1056/NEJMoa2505928
3. Mosenzon O, Alguwaihes A, Leon JLA, et al. CAPTURE: a multinational, cross-sectional study of cardiovascular disease prevalence in adults with type 2 diabetes across 13 countries. Cardiovasc Diabetol. 2021;20:154. doi: 10.1186/s12933-021-01344-0.
4. Are obesity drugs the next blockbusters? BioPharm International. Accessed August 28, 2026.