Narrative review synthesizing current evidence on tirzepatide's cardiovascular mechanisms, clinical efficacy from SURPASS-CVOT and SUMMIT trials, and therapeutic implications for heart failure management with emphasis on obesity-related HFpEF. Covers tirzepatide's effects on weight, lipids, blood pressure, inflammation, and endothelial function as interconnected HFpEF pathophysiology drivers. Provides a cardiology-focused synthesis for tirzepatide's HFpEF management role—helping cardiologists understand how tirzepatide's multi-target metabolic effects address the complex pathophysiology of obesity-driven HFpEF more comprehensively than single-mechanism agents.
Abstract
BACKGROUND: Tirzepatide, a dual GIP/GLP-1 receptor agonist, offers a novel cardiometabolic strategy beyond glycemic control with important implications for heart failure care. By producing potent, sustained weight reduction and favourable changes in lipids, blood pressure, systemic inflammation and endothelial biology, tirzepatide targets central pathophysiologic drivers of obesity-related HFpEF.
METHODS: We conducted this review to synthesise current evidence on the mechanisms, clinical efficacy and therapeutic implications of tirzepatide for heart failure management, with emphasis on obesity-related HFpEF, cardiorenal effects and safety considerations. Randomised clinical programmes and the SUMMIT outcomes trial have demonstrated symptomatic and functional improvements, reverse cardiac remodelling on imaging, reduced circulating markers of myocardial stress and fewer worsening heart-failure events versus placebo, alongside signals of renal stabilisation.
RESULTS: The tolerability profile aligns with the GLP-1 class, with gastrointestinal events predominating and a low risk of clinically important hypoglycemia; biliary events may be more likely at higher doses, while pancreatitis risk has not been clearly elevated. Data in HFrEF remain limited and caution is advised given prior mixed results with incretin therapies and theoretical concerns about rapid weight loss in advanced systolic failure.
CONCLUSION: This review integrates mechanistic insights and contemporary trial evidence to clarify how dual incretin agonism may modify the trajectory of obesity-driven heart failure, to inform multidisciplinary clinical decision making, and to highlight key unanswered questions and research priorities needed to define tirzepatide's full role in heart failure management.