Thakker · Pharmacoepidemiology and drug safety 2016 · Systematic review and network meta-analysis · n=29 trials (163,039 participants; 141,863 non-diabetic)

Statin use and the risk of developing diabetes: a network meta-analysis.

Cited 143 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and network meta-analysis of randomized controlled trials

PubMed 27277934 · doi:10.1002/pds.4020 · record verified 2026-08-28

What was done

The authors conducted a systematic literature review and frequentist network meta-analysis (NMA) evaluating the association between statin use and incident diabetes. Searches covered PubMed, Embase, and Cochrane (August 2010 to June 2014), bibliographies of pre-2010 meta-analyses, and ClinicalTrials.gov for unpublished data. Both direct pairwise meta-analyses and network meta-analyses were performed comparing individual statins and doses.

What was found

Across 29 randomized trials comprising 163,039 participants (141,863 non-diabetic at baseline), direct pairwise meta-analysis of 18 RCTs showed statins as a class significantly increased the odds of developing diabetes by 12% (OR 1.12, 95% CI 1.05–1.21; I² = 36%; p = 0.002). In the NMA, atorvastatin 80 mg carried the highest risk (OR 1.34, 95% CI 1.14–1.57), followed by rosuvastatin (OR 1.17, 95% CI 1.02–1.35). Other statin regimens did not reach statistical significance: simvastatin 80 mg (OR 1.21, 95% CI 0.99–1.49), simvastatin (OR 1.13, 95% CI 0.99–1.29), standard atorvastatin (OR 1.13, 95% CI 0.94–1.34), pravastatin (OR 1.04, 95% CI 0.93–1.16), lovastatin (OR 0.98, 95% CI 0.69–1.38), and pitavastatin (OR 0.74, 95% CI 0.31–1.77). High-dose atorvastatin significantly increased the odds of diabetes compared with pravastatin, simvastatin, and lower-dose atorvastatin.

Why it matters

This study provides comparative evidence that the diabetogenic risk of statins is molecule- and dose-dependent, predominantly driven by high-intensity regimens such as atorvastatin 80 mg and rosuvastatin.

Limits

Several individual statin comparisons lacked precision, with wide confidence intervals that approached or crossed 1.0 (particularly for pitavastatin and lovastatin). The abstract does not specify whether definitions of incident diabetes were standardized across included trials, nor does it provide baseline metabolic characteristics or follow-up durations.

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