Abstract
Background Heart failure (HF) is a leading cause of morbidity and mortality worldwide, with limited therapeutic options targeting both cardiac function and metabolic comorbidities. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has shown potential in improving cardiovascular outcomes. Proposed mechanisms include weight reduction, improved insulin sensitivity, and natriuretic effects, all of which may benefit patients with HF. Preliminary evidence from cardiovascular outcome trials suggests tirzepatide may reduce major adverse cardiovascular events (MACE), although specific data in HF populations remain limited. Objective This study aimed to evaluate the effects of tirzepatide on echocardiographic, biochemical, functional, and metabolic parameters in patients diagnosed with heart failure. Methodology A prospective observational study was conducted at Dr. Ziauddin University Hospital, Karachi, Pakistan, over one year. A total of 100 adult patients with heart failure, either with reduced (HFrEF) or preserved ejection fraction (HFpEF), who were prescribed tirzepatide, were enrolled. Clinical, biochemical, and functional assessments were performed at baseline and six months. Key parameters included left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, lipid profile, hemoglobin A1C (HbA1c), fasting plasma glucose, six-minute walk test (6MWT) distance, and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Statistical analysis was conducted using IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp., with paired t-tests. Results At six months, significant improvements were observed in LVEF (35.2% ± 6.1% to 41.5% ± 5.8%, p < 0.001) and NT-proBNP levels (2200 ± 750 pg/mL to 1400 ± 620 pg/mL, p < 0.001). Lipid parameters, including low-density lipoprotein (LDL) cholesterol (135 ± 25 mg/dL to 110 ± 20 mg/dL, p < 0.001), showed favorable changes. HbA1c decreased from 8.2% ± 1.1% to 6.9% ± 0.9% (p < 0.001). Functional outcomes improved significantly, with an increase in 6MWT distance (290 ± 60 m to 360 ± 65 m, p < 0.001) and KCCQ scores (48.5 ± 10.2 to 63.4 ± 9.8, p < 0.001). Conclusion Tirzepatide therapy was associated with significant improvements in cardiac function, metabolic control, and functional capacity in patients with heart failure. These findings highlight its potential role as an adjunctive therapy in HF management. However, to establish its long-term safety and efficacy, studies with larger cohorts and extended follow-up periods are essential, in addition to randomized controlled trials for validation.