MOHAMMED SAAD ALNAWMASI,WASAN SUWAILEM ALBALAWI,MANAR YAHYA HAYYAN,MAHA SALEEM SALEM ALHARBI,MOHAMMED ABDULHAFITH RIBI ALOTAIBI
DOI: https://doi.org/Background: Obesity and type 2 diabetes (T2D) are major contributors to cardiovascular (CV) morbidity and mortality. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has shown superior efficacy in glycemic control and weight loss compared to selective GLP-1 receptor agonists. However, its impact on CV risk in patients with obesity and T2D remains incompletely synthesized. Objective: This systematic review evaluates the cardiovascular effects of tirzepatide in patients with obesity and T2D. Methods: Following PRISMA guidelines, we conducted a comprehensive search across PubMed, Web of Science, Scopus, and Embase. Eligible studies included RCTs, cohort studies, and post-hoc analyses assessing CV outcomes (e.g., major adverse cardiovascular events [MACE], heart failure [HF] hospitalization, mortality, and biomarker changes) in adults with obesity (BMI ≥30 kg/m²) and T2D. Risk of bias was assessed using Cochrane RoB 2 and Newcastle-Ottawa Scale.
Results: Nineteen studies were included. Tirzepatide demonstrated significant CV benefits, including reduced MACE (HR 0.44–0.60), HF hospitalization (HR 0.54), and CV death/worsening HF (HR 0.62). Weight loss (12–23.4%) mediated improvements in left ventricular mass (-11 g), 6-minute walk distance (+18.3 m), and inflammatory markers (↓hsCRP, ↓NT-proBNP). Real-world studies reported lower limb event risks (HR 0.44) and superior efficacy versus GLP-1 RAs. Mechanistic studies highlighted reductions in atherogenic lipoproteins (↓apoC-III) and cardiac fibrosis. Conclusion: Tirzepatide significantly reduces CV risk in obesity and T2D, with benefits extending beyond glycemic control and weight loss to improvements in cardiac structure, atherosclerosis, and inflammation. Ongoing trials (e.g., SURPASS-CVOT) will further clarify its role in CV risk management.
