Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy: A Meta-Analysis

Study Questions:

Is intensive-dose statin therapy associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy?


The authors reviewed the literature from January 1, 1996, through March 31, 2011, to identify randomized controlled endpoint trials that compared intensive-dose statin therapy with moderate-dose statin therapy and included more than 1,000 participants who were followed up for more than 1 year. Unpublished data were obtained from investigators. Major endpoints were the numbers of participants developing diabetes and experiencing major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke, coronary revascularization). Trial-specific odds ratios (ORs) were obtained for new-onset diabetes and major cardiovascular events, and were combined using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I2 statistic.


In five statin trials with 32,752 participants without diabetes at baseline, 2,749 developed diabetes (1,449 assigned intensive-dose therapy, 1,300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1,000 patient years) and 6,684 experienced cardiovascular events (3,134 and 3,550, respectively, representing 6.5 fewer cases in the intensive-dose group per 1,000 patient-years) over a weighted mean (standard deviation) follow-up of 4.9 (1.9) years. ORs were 1.12 (95% confidence interval [CI], 1.04-1.22; I2 = 0%) for new-onset diabetes and 0.84 (95% CI, 0.75-0.94; I2 = 74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes, whereas the number needed to treat per year for intensive-dose statin therapy was 155 for cardiovascular events.


In a pooled analysis of data from five statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.


This meta-analysis supports the findings from a previous similar meta-analysis of 13 placebo-controlled statin trials involving 91,140 subjects in whom the risk of developing diabetes was 9% higher over a 4-year period in patients randomized to statins compared to placebo or standard care. Treatment of 255 patients with statins for 4 years resulted in one extra case of diabetes. The change in low-density lipoprotein cholesterol in the placebo-controlled study did not account for the variation in risk. This would suggest the increased risk of diabetes with increased statin dosing is related to other factors such as statin-associated insulin resistance. Whether the increase in fasting blood sugar will be associated with complications of type 2 diabetes is not known. Importantly, the risk of diabetes attributable to statins is small compared to the reduction in cardiovascular events.

Keywords: Myocardial Infarction, Stroke, Follow-Up Studies, Blood Glucose, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Insulin Resistance

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