Tuesday, April 24, 2007


The treatment of T2DM (type 2 Diabetes Mellitus) has progress by leaps and bounds. We have much better agents now, obviously because we have a much better understanding of diabetes, especially T2DM. One of the most exciting agents are the pPAR (peroxisome proliferator activator) gamma agonist. The most studied member is obviously rosiglitazone.

These are insulin sensitisers, meaning that they improve and increase the usefulness of endogenous insulin. Our recent understanding of T2DM is that insulin resistance plays a very important role, especially in  obese diabetics, and in metabolic syndrome. In this group of T2DM, making available more insulin (in the use of secretogogues) just makes things worse - That's another story for another day.

The first member of the insulin sensitisr group are the biguanides, of which metformin is probably their best example. Metformin unfortunately suffers from the problem of anorexia, nausea and also the danger of acidosis in patients with  renal failure.  The search or other insulin sensitisers led to the pPAR gamma agonist.

However, the use of rosigltazone was associated with the side effect of water retention and edema. The initial impression was that this water retention may be due to heart failure. This has cause some bodies to suggest that rosiglitazone or pPAR gamma agonist should not be used in patients with heart failure. The American Diabetes Association and the American Heart Association has both recommended that rosiglitazone not be used in class 3-4 heart failure, but should be safe for use in patients with class 1-2 heart failure.

A recent study by the Glasgow group led by Dr Dragie, and reported in the April 17th issue of the JACC, provides evidence for this. Dr Dragie and colleagues studied 224 patients with class 1-2 heart failure, in whom the echocardiographic LF function was </= 45%. After 1 year of rosiglitazone at 4-8 mg, the diabetics control was better, and the echocardiographic LV function remained the same. Rosiglitazone did not depress the LV myocardium. This is another of many studies to show this. It is obvious to me that rosiglitazone does not depress the myocardium, but there is some water retention side effect. Fortunately there are few other side effects.

The recently reported ADOPT study seem to suggest that rosiglitazone is also associated with a small increase incidence of fractures. This is undergoing close scrutiny at the moment.  I also noticed that this water retention side effects is more common if you use more then 4 mg of rosiglitazone. Despite this water retention side effects, rosiglitazone has proven vey useful in the control of T2DM. Rosiglitazone 's biggest side effects may in fact be their price.

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