NEW ORAL DIABETES MEDICATIONS: AN UPDATE

by Peter J. Nebergall, PhD

The pace of change is very fast in diabetes, perhaps fastest in the area of oral diabetes medications. Last issue, I discussed the different types of "oral meds," but that data may soon be out of date. Here is some new information:

Much of the new development is taking place in the class of drugs I call "insulin sensitizers," those medications acting to reduce the insulin resistance that is the central symptom of type 2 diabetes. Rezulin (troglitazone), a member of this class, has been available for several years. Now it has competition.

Novo Nordisk Pharmaceuticals Inc. offers Prandin (repaglinide), a rapid-acting, rapid-clearing, beta-cell insulin stimulator, formulated to manage meal-related glucose loads, and smooth out the "spikes" that are an unpleasant feature of type 2 diabetes. Unlike the sulfonylureas, Prandin is taken just before a meal, and has little "tail," so its effects do not linger. Prandin is intended to be used alone or in conjunction with metformin.

Takeda Pharmaceuticals America has filed with the U.S. Food and Drug Administration (FDA) for regulatory approval to market ACTOS (pioglitazone hydrochloride), a new member of the thiazolidinediones, the same class as Rezulin and Avandia. ACTOS acts to improve the body's response to its own endogenous insulin, directly reducing insulin resistance and restoring a more normal glucose response. Clinical trials of ACTOS are underway, and preliminary data are very promising. Takeda states: "When regulatory approval is received, we will co-promote ACTOS with Eli Lilly and Company."

Smith-Kline Beecham is about to offer Avandia (rosiglitazone maleate), another competitor to Rezulin. As it has been solidly proven that Rezulin works to reduce insulin resistance and improve diabetes management, it has been just as well-proven that in certain individuals, Rezulin can damage liver function, and for a very small group, that damage can be serious. Avandia, like ACTOS, is an attempt to create a safer medication, with fewer side effects.

Amylin Pharmaceuticals, Inc., has continued work on their Extendin-4 (AC2993), an analog of the hormone GLP-1, glucagon-like-peptide. This investigational diabetes drug has shown a number of potentially therapeutic effects. Extendin-4 appears to stimulate insulin secretion, except during periods of hypoglycemia (dangerously low blood sugars). It appears to modulate gastric emptying, slowing the entry of ingested nutrients into the blood. It appears it may lessen food consumption in obese animals, leading to reduction of body weight. Most important, it has resulted in "near normalization of glucose control in animal models of type 2 diabetes."

These are new, investigational or just-licensed prescription medications. Talk to your doctor about them. I list them here as an example of how unbelievably rapid is the pace of change. Where will we be two years from now? We'll be doing even better!