WHAT'S NEW IN DIABETES CARE?
Cynthia Halili-Manabat, MD, PhD
Associate Professor, MUP College of Medicine

Recently two new drugs have become available to the Filipino diabetic. The first one, Repaglinide (Novonorm), which belongs to the family of meglitinides, is an insulin secretagogue; the second, Rosiglitazone (Avandia), which belongs to the family of thiazolidenediones, is an insulin sensitizer.

Repaglinide acts by stimulating the pancreas to release more insulin. Although its mechanism of action is similar to the sulfonylureas, its chemical structure is different (it's a carbamoylmethyl benzoic acid derivative) and it acts on a separate site at the sulfonylurea receptor on the islet cell of the pancreas. Repaglinide is fast acting with a short duration of caction (of 2 hours), so it is taken right before the meal. However, if the patient decides not to eat, repaglinide is not taken and his chances of developing hypoglycemia are reduced. This so-called meal-related dosing is an advantage of repaglinide over the other sulfonylureas. Remember whem a patient takes a long acting sulfonylurea like glibenclamide, he needs to take all his meals regularly, and otherwise he may develop hypoglycemia. With repaglinide, no meal, no dose. Therefore, it works particularly well for patients who have irregular meal schedules, like the elderly.

Over the last few years, the strategy for treating diabetes has evolved. We have moved from just treating a patient to avoid the symptoms of hyperglycemia, to treating a patient with the primary objective of attaining near-normal glycemia to prevent diabetic complications. We therefore target not only normal fasting blood glucose but also normal postprandial (postmeal) blood glucoses. Like the alphaglucosidase inhibitors, acarbose and voglibose, repaglinide also target the postprandial blood glucose. It can be used as monotherapy or in combination with metformin, which is very good at targeting fasting glucoses.

Early next year, another drug in this class will become available - neteglinide (Starlix).

Rosiglitazone acts by decreasing insulin resistance and improving insulin sensitivity. It works by binding to a nuclear receptor, PPAR (peroxisome proliferator-activated receptor), enhancing the production of a number of proteins that are important in the cell's biologic response to insulin. For example, one mechanism by which rosiglitazone acts is by increasing the synthesis and translocation of the glucose transporter, GLUT-4, thereby enhancing glucose uptake into the cells. Increased glucose uptake results in reduction of blood glucose levels.

Because it is an insulin sensitizer, it needs insulin to work. It is therefore not recommended as monotherapy among type 1 diabetics. However, among type 2 diabetics, rosiglitazone can be used alone (monotherapy), or in combination with sulfonylurea, metformin, or insulin.

In clinical studies of approximately 4,600 patients treated with rosiglitazone, there was no evidence of hepatoxicity or drug-induced elevations in ALT levels. Therefore, it is not routinely recommended that ALT levels be monitored periodically in patients taking rosigllitazone. However, like in all other drugs metabolized in the liver, if the patient's baseline ALT is greater than 2.5-3 times the upper limit, rosiglitazone should not be used.

The pathogenesis of type 2 diabetes is complex, involving defects in both insulin sensitivity and insulin secretion, that ultimately result in the development of hyperglycemia. With these two new agents available in the Philippine market, the Filipino physician can better tailor his treatment to address the specific problems of his diabetic patients.