Statin-associated Diabetes Mellitus: Review and Clinical Guide

James M. Backes, PharmD; Matthew D. Kostoff, PharmD; Cheryl A. Gibson, PhD; Janelle F. Ruisinger, PharmD

Disclosures

South Med J. 2016;109(3):167-173. 

In This Article

Abstract and Introduction

Abstract

A small but significant link between new-onset diabetes mellitus (NOD) and statin therapy was noted with rosuvastatin users in the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin study. Since then multiple analyses have further confirmed this association, with most studies demonstrating a modest increase in NOD with statin therapy, especially among individuals with risk factors for developing diabetes mellitus. More recent observational analyses suggest a stronger correlation between statin use and NOD, however. A definitive mechanism confirming causation between statins and glucose impairment remains elusive, but many have been proposed. Although considered a class effect by the US Food and Drug Administration, most data indicate NOD is dependent upon the dose and potency of the statin, with certain agents appearing to be less diabetogenic.

The consensus is that the benefits of statin therapy far outweigh the risk of NOD, especially among patients with high cardiovascular risk. Nonetheless, more studies are needed to better understand this association and long-term clinical implications. In the meantime, we provide clinicians with a practical guide to assist with clinical decision making when prescribing statin therapy. Overall, this article serves to provide the primary care physician with a timely review of the most clinically relevant data regarding statins and NOD, with hopes to ultimately optimize statin prescribing and limit any potential drug-induced glucose impairment.

Introduction

Use of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) to lower low-density lipoprotein-cholesterol (LDL-C) and reducing cardiovascular (CV) events is nearing the 30-year mark. The agents have an acceptable safety profile and are the cornerstone for treating most types of dyslipidemia. The notable finding of higher rates of new-onset diabetes mellitus (NOD) among rosuvastatin users, with the 2008 publication of the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study,[1] prompted a flurry of subsequent analyses mostly supporting a small association between statins and type 2 diabetes mellitus (DM). As such, the US Food and Drug Administration and the European Medicines Agency each provided statements in 2012 indicating an association with statin therapy and reports of increased hemoglobin A1c (HbA1c) and fasting serum glucose,[2] and an increased risk of NOD in patients already at risk for DM, respectively.[3] Both agencies emphasized the risk–benefit ratio highly favoring statin use.

The association between rosuvastatin and NOD perplexed many in the medical community. Prior data from smaller studies examining statins and glucose impairment produced mixed results.[4–6] Furthermore, an analysis of the West of Scotland Coronary Prevention Study (WOSCOPS) concluded that statins may even protect against DM,[7] although this was later refuted.[8] A growing body of evidence, including newer observational analyses, suggests that the link between statins and NOD may be stronger than initially believed. This article reviews the available data regarding this association and provides clinical guidance for practitioners to minimize potential risk.

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