FDA Expands Tirzepatide Label to Reduce Cardiovascular Risk in Type 2 Diabetes

The FDA has approved a label expansion for tirzepatide (Mounjaro; Eli Lilly), a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist, to reduce the risk of major adverse cardiovascular events (MACE)—cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke—in adults with type 2 diabetes (T2D) who are at high cardiovascular risk.¹ Tirzepatide was already approved as an adjunct to diet and exercise to improve glycemic control in adults and children 10 years and older with T2D; the new indication makes it the first and only dual incretin agonist with an FDA-cleared cardiovascular risk-reduction claim.

"For people with type 2 diabetes, heart disease is the leading cause of death, and Mounjaro—the number 1 most prescribed branded type 2 diabetes medicine for adults in the US—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, Lilly Cardiometabolic Health, in a statement. "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."

The approval is based on SURPASS-CVOT (NCT04255433), a randomized, double-blind, active-comparator trial that enrolled more than 13,000 participants with T2D and established atherosclerotic cardiovascular disease across 640 sites in 30 countries, with a median follow-up of roughly 4 years.^1,2 Rather than testing tirzepatide against placebo, investigators compared it head-to-head with dulaglutide (Trulicity; Eli Lilly), a GLP-1 receptor agonist with an established cardiovascular benefit—making SURPASS-CVOT the first cardiovascular outcomes trial to pit 2 incretin therapies directly against one another.¹

Tirzepatide met the prespecified noninferiority threshold for the primary 3-point MACE end point, occurring in an estimated 12% of patients treated with tirzepatide vs 13% of patients treated with dulaglutide (HR, 0.92; 95% CI, 0.83-1.01), an 8% relative reduction that did not reach statistical superiority.² Safety and tolerability were generally consistent with tirzepatide’s established profile, with gastrointestinal adverse events—mostly mild to moderate—more common during dose escalation.^1,2

Heart disease remains the leading cause of death among people with T2D, and Eli Lilly estimates that as many as 1 in 3 adults in the US with the condition have undetected cardiovascular disease.¹ Tirzepatide is currently the top-prescribed branded T2D medicine in the US, and Lilly reported second-quarter 2026 global sales growth of 91% to $9.94 billion.^1,3 The drug is available as a once-weekly subcutaneous injection in doses ranging from 2.5 mg to 15 mg.¹

"Lilly's momentum continues, as we delivered 48% revenue growth and raised our full-year guidance," said David A. Ricks, Eli Lilly chair and CEO, in a statement.³ "At the same time, Lilly is building for the future. With our next-generation weight-loss medicine retatrutide and its complete clinical data package in hand, new manufacturing capacity coming online, and exciting new assets entering our pipeline through business development, Lilly's future, after 150 years, has never been brighter."

References

1. FDA approves Lilly's Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes. Eli Lilly and Company. News release. August 28, 2026. Accessed August 28, 2026. https://www.prnewswire.com/news-releases/fda-approves-lillys-mounjaro-tirzepatide-to-reduce-cardiovascular-risk-in-adults-with-type-2-diabetes-302862415.html
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. Lilly reports second-quarter 2026 financial results, raises full-year guidance, and highlights continued growth and pipeline progress. Eli Lilly and Company. News release. August 5, 2026. Accessed August 28, 2026. https://www.prnewswire.com/news-releases/lilly-reports-second-quarter-2026-financial-results-raises-full-year-guidance-and-highlights-continued-growth-and-pipeline-progress-302843165.html