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01 March 2010
This meta-analysis found statin therapy was associated with a small increase in the absolute risk of developing diabetes. However, for people in whom statin therapy is indicated, this risk is outweighed by the benefit of statins in the reduction of cardiovascular events.
Level of evidence:
Level 1 (good quality patient-oriented evidence) according to the SORT criteria.
Action
Health professionals should continue to follow NICE guidance on lipid modification and offer statins to people with clinical evidence of cardiovascular disease (CVD), or a 20% or greater 10-year risk of developing this. The benefits of statin therapy continue to outweigh the risks, including any small increased risk there may be of developing diabetes. Health professionals should, however, be aware of the results of this meta-analysis so they can discuss them with new and existing patients in conjunction with a discussion around likely benefits and other possible harms. The NPC patient decision aid on statins may help in these discussions.
What is the background to this?
This meta-analysis was conducted to explore whether there is any relationship between statin use and the development of diabetes, following conflicting reports from large, placebo-controlled, randomised controlled trials. Statin therapy is effective for the reduction of cardiovascular events and is generally recognised as being safe and well-tolerated. As we have previously blogged, the MHRA recently issued new advice and information on side effects of statins (such as sleep disturbance, memory loss, sexual disturbances, depression, and interstitial pneumopathy). Nevertheless, they also stated that the balance of risks and benefits of statins as a class remains positive, and that statins are one of the most important and widely used medicines in patients with lipid disorders and in the prevention of cardiovascular events.
What does this study claim?
Statin therapy was associated with a 9% increased risk for incident diabetes relative to those who hadn’t taken a statin (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.02 to 1.17). Of the 91,140 patients included in 13 trials, 2,226 assigned statins and 2,052 assigned control treatment developed diabetes during a mean of four years. This represents one additional case of diabetes per 255 (95%CI 150 to 852) patients taking statins for four years. The risk of developing diabetes with statins was highest in trials with older participants, but baseline body-mass index and change in LDL-cholesterol concentrations did not seem to be important factors.
So what?
The results of this meta-analysis show that patients taking statins were at slightly increased risk of diabetes compared with those not taking statins, and this risk seemed higher in older patients. The results only show that statins were associated with an increased risk of diabetes, not that they caused this (although this is a possibility) and the association may be due to residual confounding factors. Also, we don’t know from this study if any increase risk of developing diabetes resulted in a detrimental effect on patient-oriented outcomes, i.e. did them developing diabetes prevent them living longer or better?
Whatever the cause, in absolute terms, the increased risk of diabetes is small, especially in relation to the reduction in cardiovascular events seen with statins. In this meta-analysis, one additional case of diabetes was seen per 255 patients taking statins for four years. The authors calculated that, using data from the Cholesterol Treatment Trialists (CTT) meta-analysis of statin trials in 71,370 non-diabetic patients, statins are associated with a reduction in major coronary events of 5.4 events per 255 patients treated for four years (this is compared with control therapy for a 1mmol/L reduction in LDL-cholesterol).
In view of the evidence for benefit with statins, the authors argue that the small excess risk of incident diabetes is favourably balanced by cardiovascular benefit. Therefore, these results should not change clinical decision making in patients for whom statins are indicated. NICE guidance on lipid modification states that statins should be offered to people with clinical evidence of CVD, or a 20% or greater 10-year risk of developing this; and this guidance remains appropriate. For patients at lower cardiovascular risk or in patient groups in which cardiovascular benefit has not been proven, the potentially raised risk of diabetes should be taken into account if statin therapy is considered.
The authors recommend that the development of diabetes should be specified as a secondary endpoint in future large statin trials. They also suggest that screening for diabetes might be useful in patients taking statins, particularly older patients, and this would seem to be sensible advice.
Design, patients, intervention and comparison
Meta-analysis of large placebo- and standard-care-controlled trials of statins with cardiovascular endpoints. Included only trials with more than 1000 patients, with identical follow-up in both groups and duration of more than one year. Trials in patients with diabetes, organ transplants or who needed haemodialysis were excluded.
Outcomes and results
13 statin trials with 91,140 patients were included. There was little heterogeneity between trials. During a mean follow-up of four years, 4,278 patients (2,226 assigned statins and 2,052 assigned control treatment) developed diabetes. There were 174 more cases of incident diabetes in the statin group, representing a 9% relative increased risk for incident diabetes (OR 1.09; 95% CI 1.02 to 1.17). In absolute terms, this is one additional case of diabetes per 255 (95%CI 150 to 852) patients taking statins for four years; or 12.23 cases per 1000 patient-years with statins and 11.25 cases per 1000 patient-years with control therapy. 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.
Sponsorship
None
More information on statins can be found on the cardiovascular disease – lipids section of NPC.
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