Statin Therapy and the Increased Risk of Diabetes

This review demonstrates the influence of statin therapy (or cholesterol-lowering drugs) on the possibility of developing new-onset diabetes mellitus. It analyzed the extent of risk based on the dosage of statin therapy and concluded that the risk of development of new-onset diabetes rises with increased intensity of statin therapy among individuals with no history of diabetes.

Statin therapy is known to reduce cardiovascular events. Intensive statin therapy is known to further reduce cardiovascular events when compared to moderate statin therapy. However, it was not known whether the intensive use of statin might cause other risks such as development of new-onset diabetes and whether the extent of the risk is proportional to the intensity of the statin therapy. The authors state that “given the cardiovascular benefits of statins and the likely increasing use of intensive statin regimens, it is important to quantify any potential long-term risks to enable physicians and patients to make informed choices.” The authors compared the effects of intensive and moderate dose statin therapy on the development of new-onset diabetes and occurrence of major cardiovascular events by conducting a meta-analysis from relevant clinical trials (published as well as unpublished).

The data were gathered from 1,218 clinical trial databases, 30 full text articles and 753 abstracts. The total number of participants included 32,752 non-diabetic individuals. Reviewers included literature from trials with more than 1,000 participants and a minimum follow-up of one year. The trials were primarily designed to study the effect of intensive versus moderate dose statin treatment on cardiovascular outcomes. Additionally, the subsidiary data on adverse event reports of newly diagnosed diabetes (individual commencing glucose-lowering medication or fasting plasma glucose >126 mg/dL) were analyzed.

Results/Key findings
* Among 32,752 non-diabetic participants taking statin therapy, 2,749 participants developed (8.4 percent) developed diabetes. Among these, 1,449 were assigned intensive statin therapy and 1,300 assigned moderate statin therapy. Participants assigned to the intensive statin treatment had incident diabetes in 149 more cases than among those receiving moderate therapy.
* Among the 6,684 participants who experienced major cardiovascular events, 3,314 had been assigned intensive dose whereas 3,550 had taken moderate dose statin treatment. This proves the cardiovascular benefits of intensive statin therapy.
* The trend for the risk of the onset of diabetes and cardiovascular benefits remained the same irrespective of the participants’ age, high density lipoprotein cholesterol levels, and baseline fasting blood glucose levels. However, the risk for new onset of diabetes was found to be higher for participants with triglyceride concentrations below the median compared with those with higher triglyceride levels.
* Animal trials suggest that the development of muscle insulin resistance was a possible potential mechanism for statin-induced diabetes.

Shortcomings/Next steps
Analysis of the risk of statin-induced new onset diabetes was not a part of the clinical trial data. There could be some cases of undetected diabetes and therefore the extent of risk could be underestimated. Also, adverse effects due to intense statin therapy could have led to differences in routine clinical care which could result in detection bias. Overall benefits of statin therapy (cardiovascular benefits versus risk of new onset diabetes) need further research.

The study results show that statin use induces new onset of diabetes and the extent of risk is directly proportional to the dosage. Statin therapy is found to be a double-edged knife with cardiovascular benefits on the one hand and risk of diabetes on the other. Since the cardiovascular benefits of statin therapy are overwhelmingly high, coronary disease patients at a high risk for future cardiovascular events are advised to continue statin treatment, in spite of the associated risk. The authors state that since “cardiovascular risk from diabetes is modest in the first decade after diagnosis and as the benefit of statin therapy increases over time and in absolute terms with increasing age, net cardiovascular benefit in high risk individuals will still strongly favor statin therapy”. Clinicians should be vigilant about the drug-induced new onset of diabetes in patients receiving intensive statin therapy. Continuous monitoring of blood plasma glucose levels during statin therapy and adjustment of dose as per the biomedical results will help reduce the risks.

For More Information:
Risk of Incident Diabetes with Intensive-dose Compared with Moderate-Dose Statin Therapy – A Meta-Analysis
Publication Journal: Journal of the American Medical Association, June 2011
By David Preiss; Sreenivasa Rao Kondapally Seshasai, MD; University of Glasgow, Scotland and University of Cambridge, England

* FYI Living Lab Reports are a summary of the original report.

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