Statin-associated incident diabetes: a literature review

Abstract

Objective: To evaluate available evidence for incident diabetes associated with statin use and offer some practical management considerations.

Data sources: A literature search was performed using MEDLINE from 2000 to October 2013. The following MESH terms and text key words alone or in combination were included: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, HMG-CoA reductase inhibitors, statins, incident diabetes, new-onset diabetes, insulin resistance, impaired insulin secretion, meta-analysis, cohort study, and observational study.

Study selection: Analyzed studies were published in English and investigated incident diabetes associated with statin use.

Data extraction: Author consensus determined study inclusion in this review, focusing on observational studies and meta-analyses.

Data synthesis: Since the report of incident diabetes associated with rosuvastatin, an unexpected finding in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin, safety concerns with statins have emerged. Results of observational studies and meta-analyses show association of incident diabetes with statin use in patients with concomitant risk factors for diabetes. A pharmacodynamic mechanism has yet to be delineated, and individual statins may behave differently. Whether cardiovascular (CV) risk will increase with statin-associated incident diabetes remains unclear.

Conclusion: Review of current, available clinical data suggest a possible association between statin use and incident diabetes in patients with underlying diabetes risk factors. Although study data may be insufficient to change the current practice paradigm, clinicians should vigilantly monitor for incident diabetes in patients on statins. Patients with a low risk of CV disease and high risk of diabetes should reconsider statin use and focus on lifestyle management.

Keywords: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors; BMI = Body mass index; CHIBA = Collaborative Study on Hypercholesterolemia Drug Intervention and their Benefits for Atherosclerosis Prevention; CI = Confidence interval; CORONA = Controlled Rosuvastatin Multinational Trial in Heart Failure; CV = Cardiovascular; CVD = Cardiovascular disease; CrI = Credible interval; DM = Diabetes mellitus; Elderly; FCH = Familial combined hyperlipidemia; FPG = Fasting plasma glucose; GLUT1 = Glucose transporter type 1; GLUT4 = Glucose transporter type 4; HMG-CoA = 3-Hydroxyl-3-methylglutaryl coenzyme A; HMG-CoA reductase inhibitors; HOMA = Homeostasis model assessment; HOMA-IR = Homeostasis model assessmentinsulin resistance; HR = Hazard ratio; HbA1C = Glycosylated hemoglobin; IGT = Impaired glucose tolerance; ISG = Insulin-secreting granules; Incident diabetes; JUPITER = Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; LDL = Low-density lipoprotein; MESH = Medical subject headings; MI = Myocardial infarction; NNH = Number needed to harm; NNT = Number needed to treat; NS = Not significant; New-onset diabetes; ODB = Ontario Drug Benefit Database of Canada; OMID = Ontario Myocardial Infarction Database of Canada; OR = Odds ratio; PROSPER = Prospective Study of Pravastatin in the Elderly at Risk; QUICKI = Quantitative Insulin Check Index; RR = Relative risk; STELLAR = Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin; Statins; WHI = Women's Health Initiative; WOSCOPS = West of Scotland Coronary Prevention Study.