FDA approves Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes, supported by SURPASS-CVOT results.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved Mounjaro® (tirzepatide) to reduce the risk of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, in adults with type 2 diabetes who are at high risk for these events.
Mounjaro was previously approved as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes. The expanded indication adds cardiovascular risk reduction to its established role in glycemic control.
Phase 3 SURPASS-CVOT Supports the Expanded Indication
The approval was supported by SURPASS-CVOT (NCT04255433), a randomized, double-blind, Phase 3 cardiovascular outcomes trial comparing tirzepatide with Trulicity® (dulaglutide), a GLP-1 receptor agonist with established cardiovascular benefit. The results were published in the New England Journal of Medicine.
The trial randomized 13,299 participants with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD) across 640 sites in 30 countries. Participants received once-weekly subcutaneous tirzepatide or dulaglutide.
The primary endpoint was MACE-3, comprising cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.
Over a median follow-up of 210.1 weeks, tirzepatide demonstrated non-inferiority to dulaglutide for MACE-3, meeting the prespecified non-inferiority criterion of an upper 95.3% confidence limit below 1.05. The hazard ratio for time to first MACE was 0.92 (95.3% CI, 0.83–1.01; P=0.003 for non-inferiority).
MACE occurred in 12.2% of participants receiving tirzepatide versus 13.1% receiving dulaglutide. Superiority was not established (P=0.09).
Dual GIP and GLP-1 Receptor Activation
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. By activating both receptors, it affects glucose regulation, insulin secretion, appetite, and energy balance, contributing to improvements in glycemic control and body weight.
SURPASS-CVOT adds long-term cardiovascular outcomes data to the clinical profile of tirzepatide in adults with type 2 diabetes and cardiovascular risk.
Safety Findings
Safety and tolerability findings from SURPASS-CVOT were generally consistent with Mounjaro’s established safety profile. Gastrointestinal adverse events, including nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain, were among the most commonly reported events. More gastrointestinal adverse events were observed with tirzepatide than with dulaglutide.
Mounjaro carries a boxed warning for thyroid C-cell tumors based on animal studies and is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). The prescribing information also includes warnings concerning pancreatitis, hypoglycemia when used with insulin or insulin secretagogues, serious hypersensitivity reactions, acute kidney injury associated with volume depletion, severe gastrointestinal adverse reactions, diabetic retinopathy complications, gallbladder disease, and pulmonary aspiration during anesthesia or deep sedation.
Impact of the Expanded FDA Indication
The expanded indication broadens Mounjaro’s clinical role by adding cardiovascular risk reduction to its established use for improving glycemic control in type 2 diabetes.
Although tirzepatide did not demonstrate superiority over dulaglutide, SURPASS-CVOT demonstrated non-inferiority for MACE-3 against a GLP-1 receptor agonist with established cardiovascular benefit. The findings add cardiovascular outcomes evidence to the clinical profile of a dual GIP/GLP-1 receptor agonist and provide additional data relevant to cardiovascular risk management in adults with type 2 diabetes.
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About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.