A Comprehensive Review on the Cardioprotective and Nephroprotective Effects of Semaglutide, and Its Therapeutic Efficacy and Mechanisms in Cardiorenal Syndrome

Lu Ye,1– 3,* Pusong Tang,1– 3,* Haixu Wan,1– 3,* Xing Zhong,2– 4 Xin Chen,2– 4 Changzhao Liu,2– 4 Rui Huang2– 4 1Health Science Center, Hubei Minzu University, Enshi, Hubei, People’s Republic of China; 2Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People’s Republic of China; 3Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People’s Republic of China; 4Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changzhao Liu, Email [email protected] Rui Huang, Email [email protected]: Semaglutide (SEM), a GLP-1 receptor agonist (GLP-1RA), is commonly used to manage blood glucose and weight in type 2 diabetes mellituspatients (T2DM). Research indicates that SEM protects the kidneys and heart by slowing estimated glomerular filtration rate (eGFR) decline, reducing proteinuria, enhancing cardiac outcomes, and lowering cardiovascular risk. These benefits are linked to various mechanisms, including reduced oxidative stress and inflammation, anti-fibrotic effects, modulation of metabolism, inhibition of apoptosis, suppression of ferroptosis, and improved mitochondrial function for energy regulation. However, some studies have also found that SEM may potentially lead to renal impairment or even promote the progression of cardiorenal syndrome (CRS). Due to conflicting results, more animal studies and large-scale clinical trials are needed to understand SEM’s effects on CRS and its side effects, aiding in personalized treatment strategies. This review summarizes the functions and mechanisms of SEM in CRS, and highlights current research limitations and proposed directions for future studies.Keywords: semaglutide, cardiorenal syndrome, GLP-1RA, cardiovascular outcomes