Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 20 3 2025 09 30 221 230 Reenal Fairy Department of Medicine, Jinnah Sindh Medical University Laiba Ali Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan Hafsa Azam Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan Aaminah Khurram Department of Medicine, Jinnah Sindh Medical University Mohammad Shahzaib Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan Hafsa Tariq Jinnah Sindh Medical University Syeda Rashmeen Department of Medicine, Jinnah Sindh Medical University Haris Hassan Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan 2025 01 17 2025 09 16 Objective: This review evaluates the efficacy of semaglutide in reducing cardiac hypertrophy and enhancing cardiac function in mouse studies. Methods: A literature search was conducted using databases such as PubMed, Google Scholar, SpringerLink, Cochrane, Nature, JACC, and ScienceDirect. Keywords included “semaglutide,” “cardiac remodeling,” “heart failure,” “heart failure with preserved ejection fraction (HFpEF),” and “cardiac hypertrophy.” Studies involving male and female mice that discussed the effects of semaglutide on hypertrophy, oxidative stress, inflammatory markers, and cardiac remodeling were included. Data were extracted using the PICO framework. Results: Semaglutide consistently led to reductions in body weight, fat mass, tissue-specific inflammation, apoptosis, and oxidative stress in mice. It significantly alleviated cardiac hypertrophy, as evidenced by decreased heart weight and left ventricular mass, and improved cardiac output through enhanced cellular architecture. Inflammatory markers such as tumor necrosis factor α, interleukin 6, and atrial natriuretic peptide were notably reduced. Fibrosis was significantly attenuated at both molecular and histological levels, with decreased collagen deposition and lower markers such as collagen 1a1 and collagen 3a1. Oxidative stress markers NADPH oxidase 2 and malondialdehyde were reduced, accompanied by increased antioxidant enzymes, including superoxide dismutase and catalase. Additionally, semaglutide reduced apoptosis, evidenced by lower levels of Bcl-2-associated X protein (BAX) and slightly decreased caspase-3. Conclusion: The results demonstrate the significant potential of semaglutide for managing cardiac remodeling. Semaglutide showed considerable cardioprotective effects through the regulation of hypertrophy, oxidative stress, inflammation, apoptosis, fibrosis, and lipid metabolism. These benefits suggest its viability as a promising therapeutic agent for cardiac disorders. Nonetheless, more clinical trials, particularly in humans, are required to validate these findings and determine appropriate dosing. https://jthc.tums.ac.ir/index.php/jthc/article/view/2224 https://jthc.tums.ac.ir/index.php/jthc/article/download/2224/1216