Purpose of Review
This review summarizes the recent population-based studies, clinical trials, clinical metabolic studies, and genetic studies reporting the effects of statin therapy on the risk of diabetes. Recent studies aiming to explain the mechanisms how statin treatment affects insulin sensitivity and insulin secretion are also reviewed.
Statin therapy increases the risk of diabetes by 9%–12% in the two meta-analyses of statin trials and by 18%–99% in five population-based studies. Statin therapy impairs insulin sensitivity and insulin secretion based on clinical and epidemiologic studies. In vitro studies demonstrate that the most diabetogenic statins impair insulin sensitivity and insulin secretion by multiple mechanisms. Recent genetic studies suggest that the increased risk of type 2 diabetes may be partially explained by gene variants in the target genes for low-density lipoprotein cholesterol lowering drugs.
Population-based studies report higher incidence rates for diabetes in individuals on statin treatment compared with clinical trials. Incident diabetes has not been a prespecified endpoint in statin trials and glucose and/or HbA1c have not been routinely measured. Therefore, it is possible that the risk of diabetes in individuals on statin treatment has been underestimated in previous statin trials. Accumulating evidence from several statin trials, population-based studies, clinical studies, and in vitro studies suggests that pravastatin is the least diabetogenic statin, and simvastatin, atorvastatin, and rosuvastatin the most diabetogenic statins. In vitro studies have reported new findings on mechanisms how statin treatment affects insulin sensitivity and insulin secretion. In spite of diabetogenicity of different statins, the consensus is that the benefits of statins in reducing cardiovascular events clearly outweigh the risk of diabetes.