Does Pravastatin Prevent the Development of Diabetes Mellitus?
Does Pravastatin Prevent the Development of Diabetes Mellitus?
Abstract & Commentary
Synopsis: Pravastatin therapy resulted in a 30% reduction in the hazard of developing DM.
Source: Freeman DJ, et al. Circulation. 2001;103:357-362.
Most previous investigations into the relationship of pravastatin and glucose tolerance had been equivocal and have yielded inconclusive results.2-3 The West of Scotland Coronary Prevention Study (WOSCOPS) database, however, has now provided us with sufficient information to prospectively determine the effects of pravastatin therapy on the risk of developing diabetes mellitus (DM) in a specific population with follow-up data ranging from 3.5 to 6.1 years.1 Freeman and colleagues evaluated the effects of pravastatin therapy and the risk of developing DM in a total of 5974 men aged 45-64 years. During this study 139 subjects became diabetic and it was determined that, in this population, pravastatin therapy resulted in a 30% reduction in the hazard of developing DM.
Comment by Harold L. Karpman, MD, FACC, FACP
Freeman et al have determined that pravastatin was effective in preventing the onset of DM with a P value of 0.42 in the WOSCOPS cohort consisting of 5974 men. It should be noted that such therapy was effective on a long-term basis and that the subjects had, on average, normal triglyceride levels at baseline. The mechanism by which pravastatin reduces a subject’s risk of developing DM is not clear, however, the beneficial effects of pravastatin therapy on glucose-intolerant subjects had previously been shown in the CARE trial in which significant reductions in cardiovascular risks occurred in the pravastatin-treated subjects.4
Three known effects of pravastatin therapy may have played a primary role either individually or collectively in preventing the development of DM in the WOSCOPS subjects. Pravastatin therapy reduced triglycerides by an average of 12%, and since it has been known for many years that elevated triglyceride levels are associated with the development of DM,5 it is quite possible that a treatment effect mediated through a change in plasma triglyceride levels may have prevented the onset of glucose intolerance in these subjects. However, it should be noted that other lipid-lowering drugs do not appear to improve insulin resistance suggesting that triglyceride lowering in itself probably does not explain the observed effect.6 Second, pravastatin has been demonstrated to have anti-inflammatory effects and it has been postulated that the drug may interrupt the natural progression from central obesity to insulin resistance by reducing cytokine production which may be responsible for the metabolic syndrome associated with insulin resistance. Finally, improvement in endothial function seen in patients on pravastatin therapy has been shown to result in diminished capillary recruitment which may significantly influence selective tissue perfusion and thereby benefit glucose and insulin transport.7
Regardless of the exact mechanisms involved, it would appear that pravastatin therapy may have reduced the propensity of the subjects within the WOSCOPS to develop DM; this effect may have been one of the important mechanisms which contributed significantly to the observed positive cardiovascular benefits of the drug. The forthcoming results of the Prospective Study of Pravastatin in the Elderly Risk (PROSPER) trial will attempt to prospectively determine if pravastatin truly reduces the risk of developing DM in an elderly population.7
References
1. Sheperd J, et al. N Engl J Med. 1995;333:1301-1307.
2. Sheu WH, et al. Am Heart J. 1994;127:331-336.
3. Baba T, et al. Diabetes Care. 1993;16:402-404.
4. Goldberg RB, et al. Circulation. 1998;98:2513-2519.
5. Haffner SM, et al. JAMA. 1990;263:2893-2898.
6. Sane T, et al. Metabolism. 1995;44:589-596.
7. Sheperd J, et al. Am J Cardiol. 1999;84:1192-1197.
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