Clinical Inquiries

Do statins increase the risk of developing diabetes?

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EVIDENCE-BASED ANSWER:

Yes. Statin therapy produces a small increase in the incidence of diabetes: one additional case per 255 patients taking statins over 4 years (strength of recommendation [SOR]: A, meta-analysis). Intensive statin therapy, compared with moderate therapy, produces an additional 2 cases of diabetes per 1000 patient years (SOR: B, meta-analysis with significant heterogeneity among trials).

EVIDENCE SUMMARY

A meta-analysis of 13 randomized, placebo or standard of care-controlled statin trials (113,148 patients, 81% without diabetes at enrollment, mean ages 55-76 years) found that statin therapy increased the incidence of diabetes by 9% over 4 years (odds ratio [OR]=1.09; 95% confidence interval [CI], 1.02-1.17), or one additional case per 255 patients.1 The increased risk was similar for lipophilic (pravastatin, rosuvastatin) and hydrophilic (atorvastatin, simvastatin, lovastatin) statins, although the analysis wasn’t adjusted for doses used.

In a meta-regression analysis, baseline body mass index or percentage change in low-density lipoprotein cholesterol didn’t appear to confer additional risk. The risk of diabetes with statins was generally higher in studies with older patients (data given graphically).

Higher statin doses mean higher risk

A meta-analysis of 5 placebo and standard-of-care randomized controlled trials (39,612 patients, 83% without diabetes at enrollment, mean age 58-64 years) found that the risk of diabetes was higher with higher-dose statins.2 Therapy with atorvastatin 80 mg or simvastatin 40 to 80 mg was defined as intensive. Treatment with simvastatin 20 to 40 mg, atorvastatin 10 mg, or pravastatin 40 mg was defined as moderate.

At a mean follow-up of 4.9 years, intensive statin therapy was associated with a higher risk of developing diabetes than moderate therapy (OR=1.12; 95% CI, 1.04-1.22) with 2 additional cases of diabetes per 1000 patient-years in the intensive therapy group. The authors noted significant heterogeneity between trials with regard to major cardiovascular events.

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