Abstract 14642: Do Diuretics, Beta-Blockers, and Statins Increase the Risk of Diabetes in Patients with Impaired Glucose Tolerance? Insights from the NAVIGATOR Study

Abstract

Background: Beta-blockers and diuretics may increase the risk of new onset diabetes (NOD). More recent evidence suggests that statins also increase this risk. It is unknown to what degree use of these medications in patients with impaired glucose tolerance (IGT) and other CV risk factors is associated with NOD.

Methods: Using data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, we examined incidence diabetes among treatment-naïve patients at enrollment with diuretics (n=6343), beta-blockers (n=5637), statins (n=6143), and calcium channel blockers (CCBs) (n=6290). CCBs were used as a metabolically-neutral control. The relationship between receiving one of these treatments and NOD was evaluated using marginal structural models for causal inference designed to account for time-dependent confounding in treatment assignment. The development of diabetes was diagnosed by standard plasma glucose level (fasting or 2-hour post-glucose load) in all participants by protocol confirmed with glucose tolerance testing within 12 weeks after the elevated glucose value was recorded.

Result: During a median 5 years of follow-up, diuretics, beta-blockers, statins, and CCBs were started in 1425 (22.5%), 993 (17.6 %), 1474 (24.0%), and 1274 (20.3%) of patients, respectively. After adjustment for time-varying confounders, reported prescription of diuretics and statins was associated with increased risk of NOD (HR [95% CI] 1.36 [1.16-1.59] and 1.30 [1.11-1.53], respectively). Beta-blocker treatment showed a trend towards increased risk of NOD (HR [95% CI] 1.2 [1.00-1.46]). No association was found between the use of CCB and NOD (HR [95% CI] 1.14 [0.94-1.38]).

Conclusion: Among persons with IGT and other CV risk factors, diuretic and statin use was associated with an increased risk of NOD, while the use of beta-blockers was indeterminate. Our finding suggests that the risk of NOD with statins and diuretics needs to be carefully weighed against the benefits of these 2 drug classes.