Tuesday, October 28, 2008


It sounds too good to be true, that something cheaper works better than the newer drugs. I am talking about the treatment of diabetics ( T2DM, to be specific ). What do I mean? The 27th October issue of the Archives of Internal Medicine, published a study by Dr E Selvin of John Hopkins, which showed that treatment of T2DM with Metformin, resulted in a 26% reduction in CV mortality. Non of the other drugs ( including the newer, more expensive ones ) did. In fact, the data seemed to suggest that rosiglitazone ( newer and more expensive than metformin ), maybe associated with an increase in CV mortality. Although the trend was there, it did not meet statistic significance. Dr Selvin and colleagues actually did a meta-analysis of 40 diabetic trials, to see if treatment with drug improved CV mortality and all cause mortality. The various trials compared oral hypoglycemic drugs gainst each other and some with placebo. With this meta-analysis, we laern a few things. Firstly, most of the previous diabetic trials, did not use CV mortality and all cause mortality as an end point. They mostly use biochemical indices like fasting glucose and proteinuria, and fasting HBA1C, but not indices about patient hard end points. It does appear that for a longtime, diabetologists were pre-occupied with glucose levels and not the patient. Of course, it must be appreciated that hard patient end-points takes years to study. Biochemical levels takes weeks or months to study ( read cheaper to do ). The second thing that we learn is that metformin is without doubt, good for the diabetic heart. It may not be potent. In fact it is a little weak, but it does the job. The third thing that they learn was that newer is not necessary better. For some reason, no-one bothered to re-invent a newer metformin. Metformin had lost her patent. It had been shown to be a good drug and that metformin lowers CV mortality. Yet, pharmas keep trying to find newer diabetic drugs but not a metformin look-a-like. Why, I wonder. Two draw back with metformin were, firstly, it is relatively weak. It is a insulin sensitiser, but not too potent. Secondly, it causes nausea, anorexia, and sometimes vomiting. Especially in patients with renal dysfunction. Of course, in the good old days when we had phenformin, we saw some phenformin acidosis. Phenformin is no longer in use.
Whenever I get invited to international diabetic meetings, I always make it a point to encourage my diabetologist colleagues not to focus on sugar levels and biochemistry, but to do studies that use patient end-points like CVS morbidity/mortality and all cause mortality.
Be that as it may, metformin, an old drug, with many generic preparations in Malaysia, is the best drug in terms of diabetic treatment. It may not control blood sugar as well as some of the more potent drugs, but it sure help to patients to lower CV deaths. Looks like in the management of diabetics, cheaper maybe better.

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