Product Focus: Glimepiride Tablets

Author: Product Focus: Glimepiride Tablets

Clinical Update

Type 2 diabetes is a chronic metabolic disorder resulting from defects in both the secretion of insulin and its activity at the cellular level. When diet and exercise are inadequate for proper glucose control, many patients with type 2 diabetes are introduced to oral hypoglycemic agents.

The first line of therapy frequently includes the second- generation sulfonylureas, used in more than half of patients within the first 4 years following initial diagnosis. The importance of compliance cannot be understated—when noncompliance exceeds 25%, there is a statistically significant increase in emergency room visits, hospitalization, and total health care expenses.

Glimepiride, a member of the second generation of sulfonylureas, is used as an adjunct to diet for the management of type 2 diabetes.

Pharmacology

The sulfonylureas emerged as a class of hypoglycemic agents in 1956. The first-generation agents caused profound hypoglycemia and are rarely in use today. The second-generation sulfonylureas, including glimepiride, have shorter durations of action and are generally associated with fewer side effects.

In theory, sulfonylureas act as potassium channel blockers on the pancreatic beta cells, allowing an influx of calcium. The influx of calcium causes an increase in insulin release. For a sulfonylurea drug to be effective, therefore, there must be some pancreatic function. Generally, patients with a fasting blood plasma glucose level of 126 to 200 mg/dL will respond to monotherapy of glimepiride in addition to dietary management.

Glimepiride also decreases glucagon and hepatic gluconeogenesis, while increasing insulin binding to target receptors. After 2 weeks, both fasting and 2- hour postprandial glucose levels are significantly lower with glimepiride, and hemoglobin A1C (HbA1C) can be expected to drop by 2%. In healthy test patients, mild hypoglycemic activity is seen following a single oral dose as low as 0.5 mg.

Dosing and Administration

There is no standard dosing regimen for glimepiride; in fact, short-term use may be sufficient during transient loss of control among patients usually managing their diabetes by diet alone. No transition period is needed when converting to glimepiride from other second-generation sulfonylureas.

Glimepiride is quickly absorbed within 1 hour after oral administration, with its maximum hypoglycemic effect seen within 2 to 3 hours. The usual starting dose of glimepiride is 1 to 2 mg once daily, with breakfast or the first main meal. Maintenance dosing usually is 1 to 4 mg daily, with the maximum recommendation being 8 mg. Dosing increases should not be by more than 2 mg at 1-to 2-week intervals, based on patient response. HbA1C values should be monitored every 3 to 6 months.

In the presence of renal insufficiency, patients often demonstrate adequate control of blood glucose at doses of 1 mg daily.

Safety Profile and Drug Interactions

Nonsteroidal anti-inflammatory drugs potentiate the hypoglycemic effect of sulfonylureas such as glimepiride, as will other highly protein-bound drugs, such as salicylates, sulfonamides, chloramphenicol, warfarin, probenecid, monoamine oxidase inhibitors, and beta-blockers. Other drugs produce hyperglycemia and can represent challenges to glucose control with glimepiride. These drugs include diuretics, corticosteroids, thyroid derivatives, estrogens, phenytoin, niacin, calcium channel blockers, sympathomimetics, and isoniazid.

Glimepiride may be used in conjunction with metformin, thiazolinediones, or acarbose when any lone agent is not able to provide adequate control of glucose levels. Although these combinations can achieve tighter glycemic control, there is an increased risk of hypoglycemia.

Outlook

The increase in incidences of type 2 diabetes stems from a combination of sedentary lifestyles and genetic predisposition. Although a dramatic increase in type 2 diabetes has occurred among those over age 50, a recent concern is the spread of this former "adult-onset" diabetes into the teenage demographic.

Second-generation sulfonylurea drugs, such as glimepiride, enhance the effectiveness of diet and exercise in controlling this form of diabetes in the adult diabetic population.

Glimepiride is manufactured in 1-, 2-, and 4-mg tablets by Prasco Laboratories.

Mr. Middleton is an instructor of pharmacology for Kellogg Community College in Battle Creek, Mich.