The Lancet

Volume 375, Issue 9716, Pages 735 – 742, 27 February 2010

Prof Naveed Sattar PhD a , Dr David Preiss MRCP a , Heather M Murray MSc b, Paul Welsh PhD a, Prof Brendan M Buckley FRCPI c, Anton JM de Craen PhD d, Sreenivasa Rao Kondapally Seshasai MD e, Prof John J McMurray MD a, Dilys J Freeman PhD f, Prof J Wouter Jukema MD g, Prof Peter W Macfarlane DSc h, Prof Chris J Packard DSc h, Prof David J Stott MD h, Prof Rudi G Westendorp MD i, Prof James Shepherd MD h, Prof Barry R Davis PhD j, Sara L Pressel MS j, Prof Roberto Marchioli MD k, Prof Rosa Maria Marfisi MS k, Prof Aldo P Maggioni MD l, Prof Luigi Tavazzi MD m, Prof Gianni Tognoni MD k, Prof John Kjekshus MD n, Prof Terje R Pedersen MD o, Thomas J Cook MS p, Prof Antonio M Gotto MD q, Prof Michael B Clearfield DO r, John R Downs MD s, Prof Haruo Nakamura MD t, Prof Yasuo Ohashi MD u, Prof Kyoichi Mizuno MD v, Kausik K Ray MD e, Prof Ian Ford PhD

 Summary  Background

Trials of statin therapy have had conflicting findings on the risk of development of diabetes mellitus in patients given statins. We aimed to establish by a meta-analysis of published and unpublished data whether any relation exists between statin use and development of diabetes.

Methods

We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1994 to 2009, for randomised controlled endpoint trials of statins. We included only trials with more than 1000 patients, with identical follow-up in both groups and duration of more than 1 year. We excluded trials of patients with organ transplants or who needed haemodialysis. We used the I2 statistic to measure heterogeneity between trials and calculated risk estimates for incident diabetes with random-effect meta-analysis.

Findings

We identified 13 statin trials with 91 140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1·09; 95% CI 1·02—1·17), with little heterogeneity (I2=11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150—852) patients with statins for 4 years resulted in one extra case of diabetes.

Interpretation

Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events. Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not change.