A Clinical Review on HMG-CoA Reductase Inhibitors (Statins)-induced Hyperglycemia and New-onset Diabetes Mellitus (NODM)

Introduction: Due to their potent lipid-lowering capabilities, 3-hydroxy-3- methylglutyryl-coenzyme A (HMG-CoA) reductase inhibitors, commonly referred to as statins, are widely utilized for the primary and secondary prevention of cardiovascular disease. However, there is growing evidence that statin use may be associated with an increased risk of hyperglycemia and new-onset diabetes mellitus (NODM). This narrative review aims to summarize current understanding of statin-induced NODM by examining clinical data, potential mechanisms, risk factors, and the clinical consequences of statin-induced diabetes and hyperglycemia. Methods: A comprehensive literature search was conducted using online databases such as Medline/ PubMed/PMC, Scopus, Web of Science, and Google Scholar, as well as reference lists, to locate clinical evidence on statin-induced NODM. Meta-analyses, observational studies, and randomized controlled trials (RCTs) were assessed. Results: Several randomized controlled clinical trials, meta-analyses, and observational studies examined the incidence of NODM associated with statin therapy. Seven clinical studies and 25 meta-analyses have been included in this current review. Discussion: Long-term statin users were found to have a higher risk of NODM, according to the JUPITER, WOSCOPS, PROSPER, PROVE-IT TIMI 22, and ASCOT-LLA studies. Furthermore, several meta-analyses found a connection between statin use and a higher risk of NODM. Conclusion: Based on the clinical studies and meta-analyses included in this review, the risk of occurrence of NODM among long-term statin users was found to be higher. The review examined several potential mechanisms, such as altered glucose metabolism, decreased insulin sensitivity, and impaired insulin secretion. Risk factors such as age, obesity, high-intensity statin regimens, and pre-existing impaired glucose tolerance are covered in detail. To maximize patient results, a customized strategy to statin prescription and treatment is essential, even if the cardiovascular benefits of statins typically outweigh the risk of NODM, particularly in high-risk individuals.