Abstract

Introduction: Statin use in non-diabetic patients is associated with an increased risk of development of new-onset diabetes mellitus (NODM). However, little is known if baseline hemoglobin A1c (HbA1c) can affect diabetogenic risks and mortality benefits of statin therapy. Methods: In a retrospective cohort study between 01/2011 and 12/2018 we collected the data of 152358 non-diabetic US veterans on statin and not on statin therapy who had available baseline HbA1c value and full demographic and clinical information prior to DM diagnosis. The risk of statin-induced DM and all-cause mortality rate were assessed in the whole cohort and based on baseline HbA1c categories: ≤5.6%, 5.7-5.9% and 6.0-6.4%. DM rate and mortality rate were calculated by Cox proportional hazards model adjusted for case-mix. Results: After mean follow up of 6.89 (SD 2.26) years in non-statin users and 3.85 (SD 2.29) years in statin users and adjustments for multiple covariates such as age, gender, ethnicity, obesity, hypertension (HTN), cardiovascular disease, and metformin use, we found that the rate of statin-induced DM depends on baseline HbA1c (Table 1). Analysis by HbA1c categories showed that NODM rate is inversely related to HbA1c level, while statin use in patients with HbA1c 6.0-6.4% was not associated with increased rate of NODM. We did not observe increase in all-cause mortality in statin users and statin users with HTN across HbA1c categories. Atorvastatin use was associated with decrease in all-cause mortality in HTN patients (Table 1). Conclusions: The results of this largest to date analysis of non-diabetic US veterans closely matched for baseline characteristics suggest that the rate of statin-induced DM depends on baseline HbA1c. The significant increase in NODM rate is only observed in patients with baseline HbA1c <6.0% regardless of statin type prescribed. The increased NODM risk is not associated with all-cause mortality in statin users in general including patients with HTN.

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