Peter Libby, MD 

The Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study tested the hypothesis that targeting statin therapy on the basis of inflammatory status could provide an effective way of identifying individuals without prior cardiovascular (CV) disease, otherwise considered at low risk of CV events, who could nonetheless benefit from therapy. The study showed overwhelming benefit for the individuals in the group treated with rosuvastatin 20 mg per day who were selected for participation in the study because they had no prior CV disease, an LDL-C level <130 mg/dL, but evidence of smoldering inflammation as gauged by a high sensitivity C-reactive protein (hsCRP) ≥2 mg/L.¹ The primary publication of this study pointed out a statistically significant increase in investigator-identified new-onset diabetes. A1C during the trial was 5.8% in the placebo group and 5.9% in the rosuvastatin group, a modest difference, but one that was statistically significant as more than 17,000 individuals participated in this study, yielding considerable statistical power. 

After publication of JUPITER, a number of well-conducted meta-analyses established that all statins tested accelerate the development of diabetes.^2,3 The risk of developing new-onset diabetes appeared approximately proportional to the degree of LDL-lowering efficacy of the statins.  

These results led to widespread concern among the medical community and the general public regarding the potential of statins to “cause” diabetes. In 2012, the US Food and Drug Administration issued a public statement affirming “a small increased risk of raised blood sugar levels and the development of type 2 diabetes” in association with the use of statins.⁴  

The JUPITER data set provided an opportunity to answer two critically important clinical questions regarding statins and diabetes: (1) are certain individuals at particular risk for developing diabetes, and (2) do individuals who develop diabetes show net health benefit from statin treatment? The recent Lancet publication from the JUPITER investigators provided answers to these key queries.⁵ Those who developed diabetes in JUPITER were “on the road” to this diagnosis, having one or more major risk factors for developing diabetes. Those with no risk factors for diabetes, and with A1C in the normal range at baseline, did not have an increased risk of developing diabetes. Indeed, the data showed that individuals randomized to rosuvastatin developed diabetes just 5.4 weeks earlier than their placebo-treated counterparts. The patients with major risk factors for diabetes enjoyed as much CV event and death reduction as those without such risk factors, indicating that the benefits of statin therapy exceed the diabetes hazard—including in individuals who had a high risk of developing diabetes.  

These data should put the diabetes risk from statin therapy in perspective. Lifestyle modification remains the cornerstone of risk reduction for both diabetes and atherosclerotic CV disease events. But in my weighing of the evidence, withholding statins from individuals at risk for or with diabetes, who meet current criteria, deprives them of a treatment with the potential of reducing heart attack, stroke, and death.  

References
1. Ridker PM, Danielson E, Fonseca FA, et al; for the JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207.
2. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-742.
3. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):2556-2564.
4. FDA. FDA expands advice on statin risks. Available at: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm293330.htm. Accessed September 5, 2012.
5. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380(9841):565-571. 

Peter Libby, MD, is Chief, Cardiovascular Medicine at Brigham and Women’s Hospital and Mallinckrodt Professor of Medicine at Harvard Medical School in Boston, Massachusetts. 

Dr Libby is an unpaid consultant or involved in clinical trials for Amgen, AstraZeneca, Genzyme, GlaxoSmithKline, Merck, Novartis, Pfizer, ProNova and Sigma-Tau; he is a member of the scientific advisory boards for Athera Biotechnologies, Carolus Therapeutics, Interleukin Genetics, and BIND Biosciences. 

The pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual package inserts for use outside of the United States. 

September 2012  

This content was not associated with funding via an educational grant or a promotional/commercial interest.