Magazine article Drug Topics

New Hypoglycemic Offers Diabetic Patients Several

Magazine article Drug Topics

New Hypoglycemic Offers Diabetic Patients Several

Article excerpt

Different but the same! That would be one way to describe the newest oral hypoglycemic aRent-approved for the treatment of noninsulin-dependent diabetes mellitus as monotherapy and in conjunction with glucophage (Metformin, BristolMyers Squibb) if either agent is unsuccessful when used alone.

Manufactured by Novo Nordisk, Prandin (repaglinide) is similar to sulfonylureas in its ability to stimulate insulin secretion from the beta cells of the pancreas. But the agent-a first arrival from the meglitinide class-appears to be quite different in structure, clearance, and other features.

John Whisnant, M.D., v.p. of clinical development, Novo Nordisk, noted that sulfonylureaseven at low doses-continuously stimulate release of insulin from the pancreas. But repaglinide's actions he disclosed, are glucose dependent and are therefore "cut off at very low sugar concentrations." Although a direct relationship has not been proved, Whisnant believes this mechanistic feature may be responsible for the drug's relatively low incidence of hypoglycemia.

Repaglinide may also offer the possibility of a more prolonged use than that generally seen with other oral hypoglycemics. Maria Deutsch, R.Ph., M.S., certified diabetic educator and former ambulatory care clinical R.Ph. at the V.A. Medical Center in East Orange, N.J., noted that patients seen at her clinic typically "burned out" on sulfonylureas after five to seven years of therapy.

"Theoretically, that's due to constant beta cell stimulation," explained Whisnant. Since repaglinide appears to exhibit intermittent effects-allowing the pancreas a rest period in between doses-the time to burn-out may be extended. Long-term natural history studies have yet to confirm the theory.

Another differentiating factor is repaglinide's pharmacokinetic (PK) profile. Unlike sulfonylureas, repaglinide produces a rapid onset of action, and it is cleared rapidly from the bloodstream.

These PK parameters make the drug ideal for management of prandial (meal-related) glucose loads. And indeed, repaglinide was developed specifically for that use. The company emphasized that patients are to take each dose with meals, either two, three, or four times daily. Exact time of administration may vary from immediately preceding a meal to up to 30 minutes before the meal. Patients who add or skip a meal should add or skip a dose for that meal.

Due to its multiple and rather complex dosing schedule, the "drug should be geared toward patients who are considered independent, responsible, and have a fairly good understanding of their diabetes," noted Deutsch. …

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