Thiazolidinediones which include Rosiglitazone (Avandia) and Pioglitazone (Actos) are widely used all over the world to treat type 2 diabetes mellitus. They have been in the news recently, mainly due to two separate articles published in The New England Journal of Medicine and Diabetes Care.
Nissen and colleagues1 published meta analysis of 42 trials which showed a significant increase in the risk of myocardial infarction and a borderline increase in the risk of death from cardiovascular causes. Because the use of rosiglitazone is widespread, the public health impact of this is significant.
So what is cause of this increased risk of cardiovascular events? Many reasons can contribute to this
- Mean increase in LDL cholesterol
- Increased incidence of cardiac failure. A teleo-analysis in Diabetes Care shows a significant increase in cardiac failure at high and low doses and was not limited to elderly.2
- Possible reduction in haemoglobin
The ongoing trial on the effect of rosiglitazone on cardiovascular outcomes3 will hopefully give us a clear answer.
(1) Nissen SE, Wolski K. Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. N Engl J Med 2007; 356(24):2457-2471.
(2) Singh S, Loke YK, Furberg CD. Thiazolidinediones and Heart Failure: A Teleo-Analysis. Diabetes Care 2007.
(3) Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Dargie H et al. Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol. Diabetologia 2005; 48(9):1726-1735.
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