Tirzepatide and the Cardiovascular Continuum: Metabolic, Cardiorenal and Heart Failure Evidence

Tirzepatide is a first-in-class, once-weekly dual GIP and GLP-1 receptor agonist approved for type 2 diabetes and obesity. Given the tight link between hyperglycemia, adiposity, and cardiovascular disease, tirzepatide has rapidly gained interest as a broader cardiometabolic intervention. This narrative review summarizes mechanistic rationale and clinical evidence on cardiovascular risk-factor modification, cardiorenal signals, and outcome data. Across the SURPASS program in type 2 diabetes, tirzepatide produces large, dose-dependent reductions in HbA1c and substantial weight loss, with consistent benefits versus active comparators. In obesity, the SURMOUNT trials showed marked and durable weight reduction over long follow-up, with clinically relevant improvements in waist circumference, blood pressure, triglycerides, and inflammatory biomarkers. Beyond weight and glycaemia, available data suggest favorable effects on lipids, ambulatory blood pressure, inflammatory markers, and kidney-related endpoints in exploratory analyses. Tirzepatide also improves obstructive sleep apnea severity in adults with obesity. Regarding cardiovascular outcomes, SURPASS-CVOT supports cardiovascular safety by demonstrating noninferiority versus dulaglutide for 3-point major adverse cardiovascular events in patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD). In obesity-related HFpEF, SUMMIT shows reductions in worsening heart failure (HF) events and improvements in health status, supporting a phenotype-specific role in HF. Overall, tirzepatide is emerging as a key therapeutic option for integrated cardiometabolic risk reduction, with ongoing research needed to define its incremental benefit versus established GLP-1 receptor agonists, long-term effectiveness in routine care, and optimal positioning across HF phenotypes.