Purpose of Review <p>This review explores the relationship between lipid-lowering therapies, particularly statins, and the risk of new-onset diabetes (NOD). It examines the underlying mechanisms and evaluates whether other lipid-lowering agents present similar risks.</p> Recent Findings <p>Recent meta-analyses further underscore a dose-dependent increase in NOD risk with statin therapy, particularly with high-intensity statins. In contrast to other LDL-cholesterol lowering drugs and their impact on lipid metabolism in the liver, genetic and experimental studies indicate that statins may impair insulin secretion through various mechanisms, including alterations in small G protein function, calcium signaling, and cholesterol homeostasis in pancreatic beta cells. This might contribute to the increased risk of NOD.</p> Summary <p>Statins effectively reduce cardiovascular events but increase the risk of NOD, potentially via intracellular pathways affecting liver and beta-cell function. Despite the cardiovascular benefits of statins, personalized treatment strategies and alternative lipid-lowering therapies may offer safer options for patients at risk of diabetes, potentially shaping future clinical guidelines and therapeutic approaches.</p>