Study Title:

Statins and Type 2 Diabetes Risk - Meta Analysis

Study Abstract

Context A recent meta-analysis demonstrated that statin therapy is associated with excess risk of developing diabetes mellitus.

Objective To investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy.

Data Sources We identified relevant trials in a literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (January 1, 1996, through March 31, 2011). Unpublished data were obtained from investigators.

Study Selection We included randomized controlled end-point trials that compared intensive-dose statin therapy with moderate-dose statin therapy and included more than 1000 participants who were followed up for more than 1 year.

Data Extraction Tabular data provided for each trial described baseline characteristics and numbers of participants developing diabetes and experiencing major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke, coronary revascularization). We calculated trial-specific odds ratios (ORs) for new-onset diabetes and major cardiovascular events and combined these using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I2 statistic.

Results In 5 statin trials with 32 752 participants without diabetes at baseline, 2749 developed diabetes (1449 assigned intensive-dose therapy, 1300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1000 patient-years) and 6684 experienced cardiovascular events (3134 and 3550, respectively, representing 6.5 fewer cases in the intensive-dose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 (95% confidence interval [CI], 1.04-1.22; I2 = 0%) for new-onset diabetes and 0.84 (95% CI, 0.75-0.94; I2 = 74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number needed to treat per year for intensive-dose statin therapy was 155 for cardiovascular events.

Conclusion In a pooled analysis of data from 5 statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.

From press release:

High-dose use of Crestor, Zocor and other similar cholesterol drugs can increase the risk of developing diabetes, according to the findings of a new study.
European researchers report that high-dose regimens of a class of drugs known as statins may be linked to the onset of diabetes in rare cases, although the drugs do lower the risk of cardiovascular disease. The results of the study were published online this week by the Journal of the American Medical Association.

The researchers looked at five studies involving a total of 32,752 subjects. All were given statin-based cholesterol drugs, but half were given high doses of about 80 mg per day and the other half were given lower doses of 20 to 40 mg per day for an average of about five years. They found that more participants given high doses developed diabetes than those who were given lower doses.

The rate of diabetes was 1 in 498 among those given higher doses of drugs like Crestor, Zocor, Vytorin, Lipitor, Mevacor and Pravachol.

The study is a follow-up to a previous meta-analysis published in February 2010 in the Lancet by the same researchers. That report indicated there was about a 9% increase in the risk of type 2 diabetes among those who use statins. Another study published in March in the Journal of the American College of Cardiology found that some statins could increase the risk of diabetes by as much as one-third.

In the latest study, the health benefits and prevention of cholesterol disease outweighed the risk of diabetes, researchers concluded.

Statins are among the best-selling drugs in the United States, with $14.5 billion in combined sales in 2008. They use the liver to block the body’s creation of cholesterol, which is a key contributor to coronary artery disease.

In addition to a possible diabetes risk, all statins have been found to carry a risk of muscle injury, known as myopathy. The muscle damage can lead to a serious and potentially life-threatening condition known as rhabdomyolysis, which can lead to severe kidney damage or kidney failure. All statins currently contain a warning that myopathy and rhabdomyolysis are rare possible side effects.

The FDA recently issued a warning that 80mg Zocor doses increase the risk of rhabdomyolysis and other muscle injuries. The warning applied to all drugs that contain simvastatin, the active ingredient in Zocor. In addition to generic Zocor equivalents, simvastatin is included in the combination cholesterol drugs Vytorin and Simcor.

Zocor (simvastatin) is a synthetic statin developed by Merck & Co., which is also widely available as generic simvastatin. Before patent protections expired in 2005, it was Merck’s best-selling drug and the second best selling cholesterol lowering drug in the world, bringing in $4.3 billion in 2005.

The FDA estimates that 2.1 million people were prescribed some drug containing an 80 mg dose simvastin in 2010.

Rhabdomyolysis from Zocor causes muscle fibers to begin to break down, releasing a protein called myoglobin, which can damage the kidneys as they attempt to filter it out of the bloodstream. Symptoms of rhabdomyolysis include muscle cramps, tenderness, stiffness, pain or spasms. The illness is usually reported in patients over 65 years of age or those who have renal impairment or uncontrolled hypothyroidism.

Study Information

David Preiss, MRCP; Sreenivasa Rao Kondapally Seshasai, MD; Paul Welsh, PhD; Sabina A. Murphy, MPH; Jennifer E. Ho, MD; David D. Waters, MD; David A. DeMicco, DPharm; Philip Barter, MD, PhD; Christopher P. Cannon, MD; Marc S. Sabatine, MD, MPH; Eugene Brau
Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy
JAMA.
2011 June
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.

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