Treatment Strategies for Type 2 Diabetes

Sulfonylureas and Repaglinide

Actions of Sulfonylureas and RepaglinideTwo currently available classes of medications that work by in-creasing insulin secretion from the pancreas are the sulfonylureas and the meglitinide repaglinide, a new-er agent. One of the major advantages of sulfonylureas is that these drugs have the capacity to act quickly in responsive patients, generally within a few days of the start of therapy. This is in contrast to metformin and thiazolidinediones, which may take up to several weeks to generate a therapeutic response. Given the time frame within which most patients have had long-standing hyperglycemia, however, it is unusual that correction needs to be so rapid. Ap- proximately 50% of patients with newly diagnosed type 2 diabetes achieve acceptable glycemic control using sulfonylureas, and the primary nonresponder rate is about 15% to 20%. Sulfonylureas work best early in the course of diabetes, when ß-cell function is still sufficient to respond to the stimulation of insulin secretion promoted by these drugs.[19]

Clinical Effects of SulfonylureasSulfonylureas have been used for decades in the United States and can be an effective treatment mo-dality for glycemic regulation. However, these drugs do not directly alleviate the block to insulin action characteristic of the underlying insulin resistance in type 2 diabetes. Evidence is scant to support claims that sulfonylureas have ex-trapancreatic effects; if such effects exist, they would most likely occur secondary to a reduction in glu-cotoxicity once glycemic control improves.

Adverse Effects of SulfonylureasThe practical clinical disadvantages of sulfonylureas include the significant risk of hypoglycemia, especially when diabetes is well-controlled, and the tendency to cause weight gain. There is long-term therapeutic failure in 30% of patients, due to a loss of ß-cell responsiveness as the severity of type 2 diabetes progresses over time.[20] There are long-standing but unproven concerns that the use of sulfonylureas may be associated with increased cardiovascular risk, due to their effects on certain potassium channels in vascular tissues as well as the pancreatic islets. However, the UKPDS demonstrated that there were no adverse effects distinguishing sulfonylureas from other treatments in the intensively treated cohort.[8]

Available SulfonylureasThe many sulfonylurea agents currently available differ in their clinical potency and recommended dose range (Table 8). The longer-acting sulfonylureas with once-a-day dosing that are widely used include the glipizide sustained-release (GITS) system (Glucotrol XL) and glimepiride (Amaryl).[21] It is important to consider that the dose of any sulfonylurea agent should be in-creased only to the middle of the FDA-approved dose range, since essentially all of the clinical benefit is realized at that point.

RepaglinideRepaglinide (Prandin) is in a new class of agents that rapidly elicit an insulin secretion response following an oral dose. This profile of action potentially allows closer control of postprandial glucose excursions. Since patients are directed not to take repaglinide when they choose to skip a meal as part of a dietary plan, they can avoid hypoglycemia that might occur with a long-acting sulfonyl-urea under similar circumstances. While this dosing schedule is recommended for the pharmacologic action of the drug, some patients find it inconvenient to remember to take multiple doses of medications during the course of the day.

Repaglinide is indicated as monotherapy or in combination with metformin. Because of its similar mechanism of action, repaglinide should not be taken along with sulfonylureas. Repaglinide is taken from 0 to 30 minutes before meals (two to four times per day) in a recommended dose range from 0.5 to 4 mg, to a maximum of 16 mg/d. As with other oral agents for treatment of diabetes, repaglinide should be used cautiously in patients with impaired liver function.[22]

Previous PageSection 6 of 12Drug Benefit Trends 11(11sb):11-34, 1999. © 1999 Cliggott Publishing, Division of SCP Communications
This is a part of article Treatment Strategies for Type 2 Diabetes Taken from "Glimepiride Amaryl Tablets" Information Blog