Potential Alteration of Statin-Related Pharmacological Features in Diabetes Mellitus

OBJECTIVE: Type 2 diabetes mellitus is a chronic metabolic disease caused by insulin resistance or insulin deficiency resulting in elevated blood glucose levels. Poorly controlled diabetes is associated with the development of cardiovascular disease and dyslipidemia. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin) are an important class of therapeutic agents used to control hyperlipidemia and prevent cardiovascular disease in diabetic and nondiabetic patients. Since the effect of diabetes on the pharmacokinetics and pharmacodynamics of drugs and toxins has been shown, the aim was to review previous studies on the efficacy of statins such as atorvastatin, simvastatin, pravastatin, pitavastatin, fluvastatin, and rosuvastatin in clinical and preclinical studies in both diabetic and nondiabetic groups. METHOD: For this purpose, Web of Science, PubMed, Scopus, and Google Scholar databases were reviewed, and related English articles published until October 2020 were included in this review article. RESULTS: The findings revealed that diabetes affected statin effectiveness through changes in pharmacokinetic parameters such as clearance and biotransformation biomarkers at mRNA and protein levels. Plasma and serum concentrations of statins were accompanied by alteration in cellular activities including oxidative stress, Akt inhibition, and endothelial nitric oxide synthase (eNOS) and phosphorylation that were reflected in changes in the adverse drug reaction profile of the differing statins. CONCLUSION: Given that dyslipidemia frequently accompanies diabetes and statin therapy is common, more clinical studies are needed regarding the effects of diabetes on the effectiveness of these drugs.