Statins and diabetes risk

STATINS are a class of drugs used to lower cholesterol levels as increased cholesterol levels have been associated with cardiovascular diseases. But recent studies in people and in animal models suggest that moderate and high-potency statins — atorvastatin, rosuvastatin and simvastatin — are associated with increased risk for diabetes, whereas pravastatin has a lower risk.

In a population-based cohort study, investigators in Canada used administrative databases to assess incident diabetes between 1997 and 2010 in 4,71,000 elderly patients (aged over 65) who were newly treated with statins (73 being the median age at treatment onset).

With pravastatin as the reference drug, the risk of new diabetes was found to be 10 per cent, 18 per cent and 22 per cent higher in participants who received simvastatin, rosuvastatin, and atorvastatin respectively. Fluvastatin and lovastatin were not associated with excess risk. While pravastatin, fluvastatin, and lovastatin did not increase the risk of diabetes at all doses, moderate and high doses of atorvastatin (over 20 mg), rosuvastatin (over 10 mg) and simvastatin (over 80 mg) were associated with higher diabetes risk. That is, low doses of these drugs or low-potency statins (fluvastatin and lovastatin) might mitigate this risk.

In his editorial comment in the online Journal Watch , Paul S. Mueller pointed out that these results were biologically plausible as simvastatin has known to diminish insulin secretion, whereas pravastatin improved insulin sensitivity and inhibited gluconeogenesis. Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates. It is one of the two main mechanisms humans and many other animals use to keep blood glucose levels from dropping too low.

The finding suggests that when total cardiovascular risk favours statin treatment, a low-dose, low-potency agent should be used to begin with. But there is also a prevalent opinion among doctors that for some high-risk patients, the benefits of high-potency statins outweigh the small absolute risk for incident diabetes.

R. Ramachandran