This week, the BMJ has published a study that adds further to the debate regarding the safety of statins. It is officially recognised that one potential adverse-effect of statins is the development of diabetes. In this study, Canadian researchers pooled the results of several studies to see if the risk of diabetes was higher in individuals (with known cardiovascular disease) taking higher potency statins rather than lower ones. It was: compared to lower potency statins, the taking higher potency ones were associated with a 15 per cent increased risk of diabetes.
Now, I should make clear that evidence assessed in this study was epidemiological in nature. This means it shows that while the review found a link between higher dose statins and increase diabetes risk, this is just an association. However, we do know from other clinical studies known as randomised controlled trials (RCTs) that statins do have a genuine capacity to cause diabetes.
Perhaps in the ideal world we would be able to rely more heavily on RCTs to judge the safety of statins. The problem is, as I wrote this week, there are many reasons why RCT-derived data is utterly unreliable in this respect. The fundamental problem is that RCTs are often designed or reported in a way that can massively downplay any hazards or harms.
A case in point, is potential hazard of diabetes. Earlier this year, saw the publication of a study which claimed that side-effects from statins were no more common than those seen in people taking placebo . Actually, as I have pointed out before, the authors of this study acknowledge several of the deficiencies in the data.
Within the discussion of this paper we find the following text:
…commercial sponsors of clinical trials may not be motivated to search exhaustively for potential side effects. One pointer towards this is that…new diagnosis of diabetes was only documented in three of the 29 trials.
Yes, you read the correctly: only in about 10 per cent of the trials assessed in this review was the development of diabetes even documented. You don’t find if you don’t look, and of course what this means is that we simply can’t rely on the RCTs to assess the diabetes risk that statins bring.
While the potential diabetes risk from statins is now established, the conventional response from those generally in favour of statin therapy has been that the benefits ‘massively outweigh’ the risks. Actually, the evidence on adverse effects is so corrupted and incomplete, this claim does not necessarily stand up at all.
The authors of the recent review question the conventional line here too, when they write that this it is based on data from “..trials specifically designed to measure cardiovascular events but where diabetes events were not recorded in a consistent or required way.”
But the authors have other questions to ask too, when they point out that while statins reduce risk of overall mortality in those with known cardiovascular disease (secondary prevention), higher potency statins do not work any better than lower one here. Bearing this in mind, the authors suggest that doctors should consider the potential diabetes risk of prescribing high potency statins to patients in the secondary prevention setting.
1. Dormuth CR, et al. Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases. BMJ 2014;348:g3244 (Published 29 May 2014)
2. Finegold JA, et al. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. European Journal of Preventive Cardiology 2014;21(4):464-74