Statins and Risk of Diabetes An analysis of electronic medical records to evaluate possible bias due to differential survival

OBJECTIVE-Two meta-analyses of randomized trials of statins found increased risk of type 2 diabetes. One possible explanation is bias due to differential survival when patients who are at higher risk of diabetes survive longer under statin treatment. RESEARCH DESIGN AND METHODS-We used electronic medical records from 500 general practices in the U.K. and included data from 285,864 men and women aged 50-84 years from January 2000 to December 2010. We emulated the design and analysis of a hypothetical randomized trial of statins, estimated the observational analog of the intention-to-treat effect, and adjusted for differential survival bias using inverse-probability weighting. RESULTS-During 1.2 million person-years of follow-up, there were 13,455 cases of type 2 diabetes and 8,932 deaths. Statin initiation was associated with increased risk of type 2 diabetes. The hazard ratio (95% Cl) of diabetes was 1.45 (1.39-1.50) before adjusting for potential confounders and 1.14 (1.10-1.19) after adjustment. Adjusting for differential survival did not change the estimates. Initiating atorvastatin and simvastatin was associated with increased risk of type 2 diabetes. CONCLUSIONS-In this sample of the general population, statin therapy was associated with 14% increased risk of type 2 diabetes. Differential survival did not explain this increased risk.