Diabetogenic Potential of Statins: Mechanisms, Risk Factors, and Clinical Significance

Introduction. The association between statin use and the likelihood of developing type 2 diabetes mellitus has been highlighted in numerous recent studies, particularly among patients with metabolic syndrome or prediabetes. The relevance of this issue is defined by the widespread use of lipid-lowering agents for the prevention of cardiovascular diseases. The aim of this study is to examine current evidence regarding the diabetogenic mechanisms of statins, assess the risk of type 2 diabetes mellitus associated with statin therapy, and identify effective approaches to patient management. Materials and methods. An analysis was conducted of publications in peer-reviewed domestic and international journals, as well as data from observational studies and randomized clinical trials addressing the issue of statin-induced diabetes. The literature search was performed using the following electronic databases: Medline (PubMed), Embase, Cochrane, Scopus, Web of Science, eLibrary, and CyberLeninka. The inclusion criteria were as follows: full-text original studies published in peer-reviewed journals; study participants aged over 18 years without diabetes mellitus at baseline; administration of statins at various therapeutic dosages; and reporting of the incidence of newly diagnosed type 2 diabetes mellitus. The exclusion criteria included: conference abstracts; case reports; studies involving patients with previously diagnosed diabetes mellitus of any type at baseline; studies in which statins were evaluated exclusively as part of fixed combinations with antidiabetic or lipid-lowering agents; and publications in which diabetes mellitus was not reported as a separate outcome. Results. It has been established that the risk of developing type 2 diabetes mellitus is associated with the degree of HMG-CoA reductase inhibition and may be mediated by impaired insulin secretion from pancreatic β-cells due to reduced synthesis of isoprenoids and coenzyme Q10, as well as by the induction of insulin resistance. A meta-analysis of 17 randomized clinical trials involving 113,394 participants demonstrated that pravastatin was associated with the lowest risk of diabetes development, atorvastatin with an intermediate risk, and rosuvastatin with a 25% increased risk. The diabetogenic potential is further elevated in patients with comorbid conditions such as obesity, impaired glucose tolerance, and chronic kidney disease. Сonclusion. The studies reviewed in this analysis indicate that statins exert a diabetogenic effect that varies depending on the specific agent and dosage used. When prescribing statin therapy to patients with metabolic risk factors, an individualized approach is essential, with careful consideration of the risk – benefit balance and close monitoring of glucose metabolism parameters. Further research is required to improve risk stratification and personalize statin selection, particularly studies focusing on long-term outcomes and molecular interactions across diverse clinical and metabolic patient subgroups.