Investigation of the Relationship of Statin Medication Use, Fasting Blood Glucose Levels and Type 2 Diabetes Mellitus.

Abstract

The ongoing surveillance of safety issues and adverse reactions associated with medication use extends beyond the completion of a clinical trial or drug development program. In February 2012, decades post the first authorization by the US Food and Drug Administration (FDA) of the first statin medication, a public safety announcement was disseminated by the FDA that warned of the potential increases in blood glucose and risk of type 2 diabetes mellitus with the use of statin therapy. This research program provides evidence of statin use and T2DM in naturalistic setting that represents actual practice patterns and ‘real life’ evidence of a treatment effect. Furthermore, biomarkers such as fasting blood glucose, fasting insulin and HOMA-IR were examined as parameters along the disease pathway. Genetic research along with the field of pharmacogenomics has also rapidly emerged and deepened our insight into an individual’s genetic architecture, interaction with medication exposure and predictability of safety or efficacy at the individual patient level. Previously identified T2DM single nucleotide polymorphism (SNPs) on glucose levels and T2DM risk before and after considering interactions with statin medication use was also investigated to identify genetically susceptible individuals who may be at higher risk of developing T2DM when prescribed statin medications. This research program was conducted in the African American, Non-Hispanic White and Hispanic populations in order to the effects of statin medication in these ethnicities and across different environmental and cultural differences providing further characterization of the safety profile for statin medications in various populations. Results from GENOA demonstrated an approximately 1.5-2-fold increase in T2DM with statin use across populations and changes in fasting blood glucose based upon different levels of education, menopause, use of antihypertensive medications and increasing age in the GENOA non-T2DM and T2DM populations. Furthermore, new discoveries of statin-by-GRS interactions resulted in increased odds of T2DM in genetically susceptible individuals. The GENOA results demonstrate the need to understand the safety of statin medications in different populations across different regions and contribute to the ongoing characterization of the safety profile for statin medications.