Researchers examined the healthcare records of more than 1.5 million older people from Ontario, Canada, to examine the association between individual statin use and new onset diabetes. Patients aged 66 and older, who started treatment with a statin from 1 August 1997 to 31 March 2010 were included in the analysis. Patients with established diabetes were excluded (identified as those receiving any anti-diabetic medicines or glucose test strips). The primary outcome was incident diabetes.
Over the 14 year study period, 471,250 patients with no history of diabetes who were newly treated with a statin were identified. Of these, 227,994 (48.3%) received a statin for primary prevention, while 243,256 (51.7%) received a statin for secondary prevention.
The researchers reported that after adjustment for known confounders, and compared with patients treated with pravastatin, those treated with atorvastatin faced a 22% increase in the risk of new onset diabetes (adjusted hazard ratio 1.22, 95% confidence interval 1.15 to 1.29, NNH 172 over a median follow up of 369 days). Additionally, an increased risk was observed among those treated with rosuvastatin (1.18, 1.10 to 1.26, NNH 210 over a median follow up of 308 days) and simvastatin (1.10, 1.04 to 1.17, NNH 363 over a median follow up of 331 days). However, treatment with fluvastatin (21.52 outcomes per 1000 person years; 0.95 (0.81 to 1.11)), and lovastatin (21.80 outcomes per 1000 person years; 0.99 (0.86 to 1.14)) had crude event rates similar to pravastatin.
In animal models, pravastatin had been shown to increase adiponectin, improvinginsulin sensitivity and inhibiting gluconeogenesis, while simvastatin reduces insulin secretion, and atorvastatin and lovastatin impair glucose tolerance. For these reasons, in February 2012 the United States Food and Drug Administration mandated labelling changes for all statins except pravastatin.
The researchers also highlighted several limitations to the study, in that other risk factors for diabetes such as increased weight, ethnicity, and family history could not be accounted for. Additionally, data on blood lipids, haemoglobin A1C concentration, or triglyceride concentrations were unavailable, and therefore could not be used for risk stratification or diagnostic purposes.
A related editorial discusses the findings of this study, suggesting that these results reflect previously reported findings. However, the authors note that each 1 mmol/L reduction in low density lipoprotein-cholesterol achieved with statin treatment results in a 21% reduction in major vascular events and 9% reduction in total mortality over four years in patients with diabetes.
The NICE clinical guideline on lipid modification currently states that for both primary and secondary prevention, a statin with the lowest acquisition cost should be considered – simvastatin 40mg daily. For primary prevention patients on drugs interacting with simvastatin, or in whom simvastatin may be contraindicated, a lower dose of pravastatin may be considered, whilst in secondary prevention patients, more potent statins may be considered. This clinical guideline is currently under review.