Statins and glycaemic control in individuals with diabetes: a systematic review and meta-analysis

Erqou S, Lee CC, Adler AI.
Diabetologia. 2014 Dec;57(12):2444-52. doi: 10.1007/s00125-014-3374-x.

Background

Since diabetes is an important risk factor for cardiovascular (CV) disease, treatment guidelines recommend that certain patients with diabetes receive moderate- or high-intensity statin therapy to prevent or delay CV disease [1-4]. Statins may, however, worsen glycaemia and increase the risk of type 2 diabetes (T2DM) [5,6], depending on the dose and type of statin.
The effect of statins on glycaemic control in patients with already existing diabetes is unclear, as conflicting results have been reported. Some of those studies were small and with short follow-up time, and/or observational, thus limiting the possibility to draw conclusions.
A meta-analysis of randomised controlled trials was now conducted to assess the effects of statin therapy on glycaemia, as measured by HbA1c, in patients with diabetes. Data of nine clinical trials, involving 9696 participants (4980 on statin, 4716 controls) were used for this analysis. Participants were followed for an average of 4 months to 5 years (weighted average: 3.6 years).

Main results

• Pooled HbA1c concentration at follow-up was 7.53% (95%CI: 7.20-7.86) in patients on statins and 7.41% (95%CI: 7.11-7.72) in the control group.
  The corresponding value of the overall pooled mean difference estimate was 1.3 mmol/mol (95%CI: 0.4-2.2).
• The pooled mean HbA1c difference was larger in studies involving only participants with T2DM (0.17%, 95%CI: 0.07-0.27) than in studies involving persons with type 1 diabetes, a mixed population or unknown diabetes type (0.03%, 95%CI: - 0.08 to 0.14).
• Moderate heterogeneity was seen among the studies (I²=54%, P=0.014), which was not explained by available study-level characteristics. A trend was seen towards a stronger effect for trials on atorvastatin as compared with those studying pravastatin or simvastatin and for trials showing a larger (>1.1 mmol/L) as compared to a smaller reduction in LDL-c (< 1.1 mmol/L).

Conclusion

This analysis shows that participants with diabetes and in particular type 2 diabetes, who receive statins, had a modestly higher mean HbA1c than participants not on statins. Possible differential effects of various statins will need to be determined in future studies, as well as the importance of type of diabetes and the degree of LDL-c reduction, as hinted to by these data.
The observed small effect of statins on HbA1c likely has little clinical impact, since the benefits of statins in patients with diabetes outweigh the possible disadvantages by far. These findings imply, however, that it may we wise to watch for worsening glycaemia in anticipation of intensifying statin treatment.

Editorial comment [7]

“The findings add weight to the growing body of evidence suggesting statin treatment is per se diabetogenic across a range of patients. (…) As the authors point out, data were unavailable on participants’ use of hypoglycaemic medication, and the range of statin drugs and dosages available was limited. It is possible that, as dysglycaemia progressed in statin-treated patients, their treating physicians may have intensified their hypoglycaemic therapy, leading to an attenuation of the observed statin–HbA1c effect. (…)
If one accepts the HbA1c changes as real, the key question raised by this study, and other recent related findings, concerns its clinical implications, if any, for the care of patients with diabetes. (…) The primary clinical value of statins lies in the prevention of macrovascular disease, an effect that is not meaningfully diminished by a small disturbance of glycaemic control. (…)The balance of benefit and risk falls, therefore, strongly in favour of continuing to prescribe statins for type 2 diabetic patients according to current guidelines. (…) Evidence such as  that presented by Erqou and colleagues for the adverse, but comparatively minor, effects of statins on glycaemia should encourage healthcare professionals to redouble their efforts to help their patients to improve their diets, engage in more physical activity and stop smoking”, as modest lifestyle improvement will help offset the dysglycaemia risk.

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