Tirzepatide Gets FDA Approval to Cut Cardiovascular Risk in Type 2 Diabetes

The US Food and Drug Administration (FDA) has approved tirzepatide (Mounjaro) to lower the risk of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal heart attack, or non-fatal stroke, in adults with type 2 diabetes at high risk for these events.

Eli Lilly and Company announced the approval on August 28, 2026, based on results from the SURPASS-CVOT trial. Tirzepatide, a dual GIP and GLP-1 receptor agonist, is already approved to improve glycemic control in adults and children ten years of age and older with type 2 diabetes.

"Heart health deserves attention throughout the course of treatment, not just after a serious cardiovascular event," David D'Alessio, MD, study co-author and director of the Division of Endocrinology and Metabolism at Duke University School of Medicine, said in a statement. "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."

The approval marks the first head-to-head cardiovascular outcomes comparison between 2 incretin therapies, rather than a placebo-controlled design. Lilly positioned the trial as a higher evidentiary bar, testing tirzepatide against dulaglutide (Trulicity), a GLP-1 agent with an established cardiovascular indication. The result gives clinicians a second incretin option carrying a MACE-reduction label alongside tirzepatide's existing glycemic and weight effects.

Tirzepatide Efficacy and Design in SURPASS-CVOT

SURPASS-CVOT was an event-driven, randomized, double-blind, phase 3 trial evaluating tirzepatide against dulaglutide in adults with type 2 diabetes and established atherosclerotic cardiovascular disease. Investigators enrolled 13,299 participants across 640 sites in 30 countries, making it the largest and longest tirzepatide trial completed to date. Participants received tirzepatide, dosed at 15 mg or the maximum tolerated dose, or dulaglutide at 1.5 mg, both administered subcutaneously once weekly.

Median follow-up reached 210.1 weeks, approximately 4 years, within a trial spanning close to 5 years. The primary objective was to demonstrate non-inferiority for MACE-3, a composite of cardiovascular death, heart attack, or stroke.

Tirzepatide met this objective, showing an 8% lower rate of MACE-3 events versus dulaglutide, with a hazard ratio of 0.92 (95.3% CI, 0.83-1.01). Superiority over dulaglutide was not established.

Tirzepatide Safety Profile in SURPASS-CVOT

The safety and tolerability profile of tirzepatide in SURPASS-CVOT remained consistent with its established profile from prior trials, according to Lilly. The most commonly reported adverse events were gastrointestinal in nature, generally mild to moderate in severity. These events occurred primarily during the dose-escalation period of treatment.

Tirzepatide carries a boxed warning for thyroid C-cell tumors, and the drug remains contraindicated in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. Beyond the boxed warning, labeled risks include pancreatitis, hypoglycemia when combined with sulfonylureas or insulin, and dehydration-related kidney complications. No new safety signals emerged from the cardiovascular outcomes data specific to the trial.

Lilly noted the findings support extending tirzepatide's established profile into this new cardiovascular indication.

"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, 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."

References

1. Eli Lilly and Company. FDA approves Lilly's Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes. Published 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. Fang M, Wang D, Tang O, et al. Subclinical cardiovascular disease in US adults with and without diabetes. J Am Heart Assoc. 2023;12(11):e029083. doi:10.1161/JAHA.122.029083