Agents that bind to sulfonylurea and stimulate insulin

(1) Glyburide

(2) Glipizide

(3) Glimepiride

(4) Gliclazide

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Well absorbed but rapidly metabolized in the liver

• Shortest duration of action (6-10 hrs)

• Best administered in divided doses

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Prolonged hypoglycemia has been reported in patients receiving certain antibacterial sulfonamide (sulfisoxazole), phenylbutazone for arthralgias, or the oral azole antifungal medications for candidiasis

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Slowly metabolized in the liver

• 20–30% is excreted unchanged in the urine

• The average maintenance dosage is 250 mg daily, given as single dose in the morning

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Prolonged hypoglycemic reactions are more common in elderly patients, and the drug is contraindicated in this group

• Other adverse effects include hyperemic flush after alcohol ingestion in genetically predisposed patients and hyponatremia

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• More slowly absorbed than the other sulfonylureas

• Half-life is about 7 hours

• Metabolized compounds retain hypoglycemic effects

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Half-life is 1 hour

• Duration of action is 8–24 hours

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Metabolized in the liver into products with very low hypoglycemic activity

• Average maintenance dosage is 5–10 mg/d given as a single morning dose

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Slightly enhances free water clearance

• Contraindicated in the presence of hepatic impairment and in patients with renal insufficiency

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Shortest half-life 2–4 hours

• For maximum effect in reducing postprandial hyperglycemia, should be ingested 30 minutes before breakfast

• Extended-release preparation (Glucotrol XL) provides 24-hour action after a once-daily morning dose (maximum of 20 mg/d)

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• 90% of glipizide is metabolized in the liver

• Contraindicated in patients with significant hepatic impairment

• Preferable in the elderly and for those patients with renal impairment

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Longer duration of action

• Approved for once-daily use as monotherapy or in combination with insulin.

• Achieves blood glucose lowering with the lowest dosage of any sulfonylurea compound

• It is completely metabolized by the liver to metabolites with weak or no activity.

Agents that bind to sulfonylurea and stimulate insulin

Sulfonylurea

• Half-life is 10 hours

• The recommended starting dosage is 40–80 mg daily

• Maximum dosage of 320 mg daily

• It is completely metabolized by the liver to inactive metabolites

Agents that bind to sulfonylurea and stimulate insulin

Meglitinide

• First member of the meglitinide group of insulin secretagogues

• Modulate beta-cell insulin release by regulating potassium efflux through the potassium channels

Agents that bind to sulfonylurea and stimulate insulin

Meglitinide

• Has a fast onset of action, peak concentration and peak effect within approximately 1 hour after ingestion

• Cleared by hepatic CYP3A4

• Plasma half-life is 1 hour

• The drug should be taken just before each meal in doses of 0.25–4 mg (maximum 16mg/d)

Agents that bind to sulfonylurea and stimulate insulin

Meglitinide

• For use in controlling postprandial glucose excursions

• Hypoglycemia is a risk if the meal is delayed or skipped or contains inadequate carbohydrate.

• Used in patients with renal impairment and in the elderly

• Approved as monotherapy or in combination with biguanides

Agents that bind to sulfonylurea and stimulate insulin

Meglitinide

• There is no sulfur in its structure, so it may be used in type 2 diabetics with sulfur or sulfonylurea allergy.

Agents that bind to sulfonylurea and stimulate insulin

Meglitinide

• Benzylsuccinic acid derivative that binds to the sulfonylurea receptor

• It has been approved for use in Japan

Agents that bind to sulfonylurea and stimulate insulin

D-Phenylalanine Derivative

• Stimulates rapid and transient release of insulin from beta cells through closure of the ATP-sensitive K+ channel

• Absorbed within 20 minutes after oral administration

• Time peak conc. <1 hour

• Metabolized in the liver by CYP2C9 and CYP3A4

• Taken before the meal and reduces the postprandial rise in blood glucose levels

Agents that bind to sulfonylurea and stimulate insulin

D-Phenylalanine Derivative

• Efficacious when given alone or in combination with non-secretagogue oral agents (such as metformin)

• It can be used in patients with renal impairment and in the elderly

• Hypoglycemia is the main adverse effect