September 9th, 2014

Lower Rate of Microvascular Complications in Statin Users Who Develop Diabetes

In recent years, the medical community has become increasingly aware that taking statins can result in slightly higher glucose levels, and this can lead to a diagnosis of diabetes in a small but statistically significant number of people. But it has been unclear whether the diagnosis of diabetes in people taking statins also places them at increased risk for the microvascular complications linked to diabetes. Now, an observational study published in the Lancet Diabetes & Endocrinology finds that among people newly diagnosed with diabetes, statin users are less likely than nonusers to develop most of these complications. (The beneficial effects of statins in reducing macrovascular complications — cardiovascular disease — in diabetics and others is well established in people at high risk for these events.) 

Danish researchers examined the rate of microvascular outcomes in more than 15,000 statin users who developed diabetes and 47,000 nonusers of statins who developed diabetes. Over a median follow-up of 2.7 years, statin users had a 40% reduction in the risk for developing retinopathy (hazard ratio 0.60, CI 0.54–0.66, p<0.0001), a 34% reduction in the risk for diabetic neuropathy (HR 0.66, 0.57–0.75, p<0.0001), and a 12% reduction in gangrene of the foot (HR 0.88, 0.80–0.97, p=0.010). There was no significant difference in the rate of diabetic nephropathy (HR 0.97, 0.85–1.10, p=0·62). The overall results were similar after adjusting for differences between the groups. In rough accord with previous research, the Danish researchers observed that statin users had a 17% increase in the risk for developing diabetes.

The authors conclude: “Whether or not statins are protective against some forms of microvascular disease, a possibility raised by these data, and by which mechanism, will need to be addressed in studies similar to ours, or in mendelian randomization studies…. Ideally, however, this question should be addressed in the setting of a randomized controlled trial.”

Commenting on the study, Darrel Francis offered an overview of the risks and benefits of statins: “For every 1000 primary prevention patients randomized to statin, 5 patients gain a diagnosis of diabetes, while 5 patients are saved from death, 10 from nonfatal myocardial infarction, and 6 from stroke. Some people find this a good deal, but others are cautious because of the justified fear of diabetes.”



One Response to “Lower Rate of Microvascular Complications in Statin Users Who Develop Diabetes”

  1. Darrel P Francis, MD FRCP says:

    Gaining a diagnosis of diabetes sounds frightening. But remember the lessons from our previous enthusiasm for strict glucose control? We all agree on encouraging excellent dietary control to lower glucose, but when we use *drugs* to lower it more strictly, we do not deliver the reduction in diabetic complications that we might expect. It is as though diabetes is an upstream phenomenon and our glucose-lowering drugs act too far downstream to prevent the most important complications.

    If many drugs that (intentionally) *lower* glucose do not correspondingly prevent diabetic complications, why should all drugs that (unintentionally) *raise* glucose be assumed to cause diabetic complications? Nielsen & Nordestgaard’s fascinating study suggests not. As the authors point out, this was an observational study, and should be formally tested by introducing microvascular endpoints into any future randomized trial of statins. If such a trial showed no net microvascular harm, it would extinguish the last major medical concern over adverse effects ( in offering statins in primary prevention.