Friday, March 29, 2013


I did not quite realise at first that 2008 was an important year, for medicine in general and for management of diabetes in particular. This was the year when news first broke out that Rosiglitazone, one of the new PPAR gamma ( PPAR stands for peroxisome proliferator activator receptor ) activator that acts on fat cells to lower glucose, fatty acids and insulin, could be cardio-toxic, causing an increase incidence of AMI. Now this was terrible news. It is well to remember that all the old oral hypoglycemic agents that we have till then, with the possible exception of metformin, had data showing effective glucose lowering, but no data showing lack of cardiac toxicity. So when rosiglitazone whistle blowers announced that the use of rosiglitazone may increase the incidence of heart attacks, US FDA reacted.

The US FDA responded by tightening the rules on oral hypoglycemic drug approval. Now lets take a step back. Before 2008, to have an oral hypoglycemic agent approve, one has to prove that the drug was safe for human consumption and that it lowers blood glucose, and later HbA1c.

I have always thought that this was improper and incorrect, because blood sugar is a chemical, lowering it not the important parameter. It must also show that by lowering it, it reduces the effects of the high blood glucose, namely reduce the incidence of MIs, the need for coronary revascularisation, strokes and end stage renal disease. In fact, I remember that on many diabetic forums, including one international one, I raise the issue to the delight of the cardiologist in the audience but the chagrin of the diabetologist present.
To cut a long story short. since 2008, the US FDA, and last year the European EMA ( European Medicines Agency - Euro equivalent of US FDA ) has insisted that for drug approval, companies must show that the anti-diabetic drug is safe for humans, and safe for the heart. Just lowering blood glucose is not good enough. Having found to be safe for the heart , it must then show that it is good for the heart.
Since 2008 tightening by US FDA, the first oral hypoglycemic agent approved is Saxagliptin ( Onglyza-AZ ). They pass the cardiac safety test and we are awaiting data on cardio-protective effect. In a meta-analysis of data from all the completed DDP4 inhibitor trials so far, DDP4 agents show be cardio-protective, with an odds ratio of 0.71, apparently. So now, all oral hypoglycemic agents seeking approval must pass the cardiac safety test.
On the one hand, this is undoubtedly good for the patient, so that we are not causing more harm then good. On the other hand, some would argue that by placing more barriers and asking for more data, must mean more research, and more cost, thereby giving the big pharmas a clear advantage.
I suppose, nothing comes free. That is partly why healthcare cost is escalating.
So US FDA in 2008, had an oversight, approved Rosiglitazone. Found that it was a mistake. In USA, Rosiglitazone is now used under severe restriction. In Europe, it is banned. Having made the mistake, now US FDA is pursuing a strategy of "hypersight", and the cost of drugs will be fewer and costlier.
This is the new world.

1 comment:

Winston said...

Doc, I understand that nowadays, sugar is being treated as a poison.
Is it necessary to lay off all refined sugar altogether?
I have also read an article that injection of stem cells can cure type 2 diabetes.
This is according to an article in the Times of India.
The injections will kick start the pancreas to increase insulin production and thereby cure type 2 diabetes.
Is that true?
Thank you.