Semaglutide for Organ Protection

This chapter examines semaglutide as a multiorgan therapeutic strategy for cardiometabolic risk reduction, with particular focus on cardiovascular disease, chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis. It integrates contemporary guidance from the American Diabetes Association (ADA) 2025 Standards of Care, the ADA/European Association for the Study of Diabetes /EASD consensus, and Kidney Disease: Improving Global Outcomes recommendations with evidence from Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes-6, Semaglutide Effects on Cardiovascular Outcomes In People With Overweight or Obesity, effect of semaglutide versus placebo on the progression of renal impairment in subjects with type 2 diabetes and chronic kidney disease (FLOW), Semaglutide Cardiovascular Outcomes Trial, and effect of semaglutide in subjects with noncirrhotic nonalcoholic steatohepatitis, alongside mechanistic literature on glucagon-like peptide-1 receptor agonist-mediated cardioprotective and nephroprotective effects. In cardiovascular prevention, semaglutide is positioned early in high-risk type 2 diabetes on the basis of risk-factor clustering, visceral adiposity, inflammation, and residual cardiometabolic risk, independent of glycated hemoglobin alone. In chronic kidney disease, the review highlights FLOW as a practice-changing kidney outcomes trial demonstrating reduction in major kidney events, slower estimated glomerular filtration rate decline, and reduction in albuminuria. In metabolic dysfunction-associated steatotic liver disease/MASH, semaglutide is presented as a clinically meaningful option for steatohepatitis resolution and fibrosis-related benefit, particularly in obesity- and diabetes-associated liver disease. Overall, the chapter supports semaglutide as an organ-protective therapy whose benefits extend beyond glucose lowering toward integrated cardiovascular, renal, and hepatic risk reduction.