What is the recommended dosage and management of Glyburide (Glibenclamide) for type 2 diabetes mellitus?

Glyburide Dosing and Management for Type 2 Diabetes

For type 2 diabetes, initiate glyburide at 2.5-5 mg once daily with breakfast, titrating by no more than 2.5 mg weekly based on blood glucose response, with a maximum dose of 20 mg daily. 1

Initial Dosing Strategy

• Start at 1.25 mg daily in elderly patients, those with renal impairment, or patients at increased risk of hypoglycemia 1
• Standard starting dose is 2.5-5 mg daily administered with breakfast or the first main meal for most patients 1
• Patients more sensitive to hypoglycemic drugs require the lower 1.25 mg starting dose 1

Titration Protocol

• Increase dosage in increments of no more than 2.5 mg at weekly intervals based on blood glucose monitoring 1
• The usual maintenance dose ranges from 1.25 to 20 mg daily, which may be given as a single dose or divided doses 1
• Maximum daily dose is 20 mg; doses exceeding this are not recommended 1

Critical Monitoring Requirements

• Monitor blood glucose periodically to determine minimum effective dose and detect primary or secondary treatment failure 1
• Monitor for hypoglycemia, which occurs in 24.3% of glyburide-treated patients compared to 4.4% with other agents 2
• Glycosylated hemoglobin (A1C) levels should be monitored to assess response to therapy 1
• Patients should test urine for glucose and acetone at least three times daily during any insulin withdrawal period 1

Special Clinical Situations

Transferring from Other Oral Agents

• Transfer conservatively with an initial daily dose of 2.5-5 mg 1
• No transition period or priming dose is necessary except when transferring from chlorpropamide 1
• Exercise particular care during the first two weeks when transferring from chlorpropamide due to prolonged drug retention and risk of overlapping hypoglycemic effects 1

Transferring from Insulin

• If insulin dose <20 units daily: substitute with glyburide 2.5-5 mg as a single daily dose 1
• If insulin dose 20-40 units daily: place directly on glyburide 5 mg daily as a single dose 1
• If insulin dose >40 units daily: decrease insulin by 50% and start glyburide 5 mg daily, then progressively withdraw insulin while increasing glyburide by 1.25-2.5 mg every 2-10 days 1

Combination with Metformin

• When adding glyburide to metformin, follow the gradual titration protocol outlined above 1
• Glyburide/metformin combination tablets (1.25/250 mg) provide superior glycemic control compared to monotherapy, achieving a mean A1C reduction of -2.27% versus -1.53% with metformin alone 3
• The risk of hypoglycemia continues and may be increased with combination therapy 1

Drug Interaction: Colesevelam

• Administer glyburide at least 4 hours prior to colesevelam to avoid reduced plasma concentration and total exposure 1

Safety Considerations and Contraindications

Hypoglycemia Risk

• Hypoglycemia is the most significant adverse effect, occurring in approximately one-quarter of patients 2
• Patients who fail to adhere to prescribed dietary and drug regimens are more prone to unsatisfactory response and hypoglycemia 1
• No patient in maximal dose studies experienced hypoglycemia in the first 2 weeks when properly monitored 4

Pregnancy: Absolute Contraindication

• Glyburide is NOT recommended as first-line treatment for gestational diabetes because it crosses the placenta (umbilical cord concentrations reach 50-70% of maternal levels) 5
• Insulin is the first-line agent for gestational diabetes in the United States 5
• Glyburide was associated with higher rates of neonatal hypoglycemia and macrosomia than insulin or metformin 5
• Glyburide failed to achieve adequate glycemic control in 23% of women with gestational diabetes 5
• Long-term safety data for offspring exposed to glyburide are not available 5

Comparative Safety Profile

• Withdrawal due to lack of efficacy or adverse events occurred more frequently with glyburide (20.8%) than pioglitazone (12.8%) 2
• Cardiac events occurred in 8.8% of glyburide-treated patients versus 4.4% with pioglitazone 2

Clinical Efficacy

• Glyburide provides comparable glycemic control to first-generation sulfonylureas but at considerably lower doses 6, 7
• A maintenance dose of 5 mg glyburide provides approximately the same blood glucose control as 250-375 mg chlorpropamide, 250-375 mg tolazamide, 500-750 mg acetohexamide, or 1000-1500 mg tolbutamide 1
• In markedly symptomatic patients with type 2 diabetes (blood glucose ≥300 mg/dL), maximal dose glyburide (10 mg twice daily in patients <65 years; 10 mg daily in patients ≥65 years) reduced blood glucose from 456 mg/dL at baseline to 120 mg/dL at 4 months, with A1C falling from 18.1% to 8.1% 4

Positioning in Treatment Algorithm

• The American Diabetes Association recommends sulfonylureas as second-line agents after metformin, typically used in combination therapy when metformin monotherapy fails to achieve glycemic targets 8
• Initial therapy should consist of lifestyle intervention and metformin 5
• GLP-1 receptor agonists and SGLT2 inhibitors are generally preferred over sulfonylureas for patients with diabetic kidney disease due to superior cardiovascular and renal outcomes 8