GLYBURIDE (MICRONIZED)

Clinical safety rating: safe

Drugs that increase hypoglycemia risk (eg beta-blockers) Can cause severe and prolonged hypoglycemia.

How it works

Binds to sulfonylurea receptor (SUR1) on pancreatic beta-cells, closing ATP-sensitive potassium channels, depolarizing the cell membrane, and stimulating insulin secretion via calcium influx.

What the body does with it

Metabolism	Hepatic metabolism via CYP2C9 to weakly active metabolites; major metabolite: 4-trans-hydroxyglyburide; minor: 3-cis-hydroxyglyburide.
Excretion	Renal: 50% as metabolites (majorly hydroxylated derivatives) and <5% unchanged; Biliary/fecal: ~30% as metabolites via bile into feces; total elimination: ~80% renal, ~20% fecal.
Half-life	Terminal elimination half-life: 5-10 hours (mean 7.2 hours); clinically, may be prolonged in hepatic impairment or renal dysfunction (half-life up to 20-24 hours in severe renal impairment).
Protein binding	99% bound to albumin; primarily to site II (the benzodiazepine/acyl-binding site) on human serum albumin.
Volume of Distribution	0.16-0.3 L/kg (mean 0.23 L/kg); clinical meaning: low Vd indicates limited extravascular distribution, consistent with high protein binding and hydrophilic nature.
Bioavailability	Oral (micronized): 100% (complete absorption from gastrointestinal tract; micronized formulation enhances dissolution and absorption).
Onset of Action	Oral (micronized): 45-60 minutes for reduction in plasma glucose; peak effect at 2-3 hours.
Duration of Action	Duration: up to 24 hours; clinical note: due to long duration, once-daily dosing is sufficient, but risk of prolonged hypoglycemia in elderly or renal impairment.

Classification & Brands

Dosing & administration

1.25-20 mg orally once daily or divided twice daily; start at 1.25-5 mg once daily, titrate every 1-2 weeks by 2.5 mg increments; maximum 20 mg/day.

Dosage form	TABLET
Renal impairment	eGFR 30-60 mL/min: start at 1.25 mg once daily, titrate cautiously; eGFR <30 mL/min: contraindicated.
Liver impairment	Mild to moderate hepatic impairment (Child-Pugh A or B): start at 1.25 mg once daily, titrate cautiously; severe (Child-Pugh C): contraindicated.
Pediatric use	Not recommended; safety and efficacy not established in pediatric patients.
Geriatric use	Start at 1.25 mg once daily; monitor glucose closely; avoid in patients >80 years if eGFR <60 mL/min unless clinically necessary.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Drugs that increase hypoglycemia risk (eg beta-blockers) Can cause severe and prolonged hypoglycemia.

FDA category	Animal
Breastfeeding	Excretion into breast milk is minimal; relative infant dose estimated at <5%. M/P ratio not well established. Monitor infant for hypoglycemia. Considered compatible with breastfeeding by AAP.
Teratogenic Risk	FDA Pregnancy Category B. No evidence of teratogenicity in animal studies. Limited human data; risk of neonatal hypoglycemia if used near term. Not recommended for use during pregnancy; insulin preferred.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Hypoglycemia
Serious Effects

Absolute Contraindications

["Type 1 diabetes mellitus","Diabetic ketoacidosis","Known hypersensitivity to glyburide or sulfonamides","Concomitant use with bosentan"]

Clinical Precautions

Precautions

["Hypoglycemia: risk increased in elderly, debilitated, malnourished, renal/hepatic impairment, or with certain drugs","Hemolytic anemia in G6PD deficiency","Possible increased cardiovascular mortality (controversial)","May cause disulfiram-like reaction with alcohol","Use with caution in renal/hepatic impairment"]

Clinical Tips & Counseling

Drug interactions

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GLYBURIDE (MICRONIZED)

Clinical safety rating: safe

Drugs that increase hypoglycemia risk (eg beta-blockers) Can cause severe and prolonged hypoglycemia.

How it works

Binds to sulfonylurea receptor (SUR1) on pancreatic beta-cells, closing ATP-sensitive potassium channels, depolarizing the cell membrane, and stimulating insulin secretion via calcium influx.

What the body does with it

Metabolism	Hepatic metabolism via CYP2C9 to weakly active metabolites; major metabolite: 4-trans-hydroxyglyburide; minor: 3-cis-hydroxyglyburide.
Excretion	Renal: 50% as metabolites (majorly hydroxylated derivatives) and <5% unchanged; Biliary/fecal: ~30% as metabolites via bile into feces; total elimination: ~80% renal, ~20% fecal.
Half-life	Terminal elimination half-life: 5-10 hours (mean 7.2 hours); clinically, may be prolonged in hepatic impairment or renal dysfunction (half-life up to 20-24 hours in severe renal impairment).
Protein binding	99% bound to albumin; primarily to site II (the benzodiazepine/acyl-binding site) on human serum albumin.
Volume of Distribution	0.16-0.3 L/kg (mean 0.23 L/kg); clinical meaning: low Vd indicates limited extravascular distribution, consistent with high protein binding and hydrophilic nature.
Bioavailability	Oral (micronized): 100% (complete absorption from gastrointestinal tract; micronized formulation enhances dissolution and absorption).
Onset of Action	Oral (micronized): 45-60 minutes for reduction in plasma glucose; peak effect at 2-3 hours.
Duration of Action	Duration: up to 24 hours; clinical note: due to long duration, once-daily dosing is sufficient, but risk of prolonged hypoglycemia in elderly or renal impairment.

Classification & Brands

Dosing & administration

1.25-20 mg orally once daily or divided twice daily; start at 1.25-5 mg once daily, titrate every 1-2 weeks by 2.5 mg increments; maximum 20 mg/day.

Dosage form	TABLET
Renal impairment	eGFR 30-60 mL/min: start at 1.25 mg once daily, titrate cautiously; eGFR <30 mL/min: contraindicated.
Liver impairment	Mild to moderate hepatic impairment (Child-Pugh A or B): start at 1.25 mg once daily, titrate cautiously; severe (Child-Pugh C): contraindicated.
Pediatric use	Not recommended; safety and efficacy not established in pediatric patients.
Geriatric use	Start at 1.25 mg once daily; monitor glucose closely; avoid in patients >80 years if eGFR <60 mL/min unless clinically necessary.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Drugs that increase hypoglycemia risk (eg beta-blockers) Can cause severe and prolonged hypoglycemia.

FDA category	Animal
Breastfeeding	Excretion into breast milk is minimal; relative infant dose estimated at <5%. M/P ratio not well established. Monitor infant for hypoglycemia. Considered compatible with breastfeeding by AAP.
Teratogenic Risk	FDA Pregnancy Category B. No evidence of teratogenicity in animal studies. Limited human data; risk of neonatal hypoglycemia if used near term. Not recommended for use during pregnancy; insulin preferred.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Hypoglycemia
Serious Effects

Absolute Contraindications

["Type 1 diabetes mellitus","Diabetic ketoacidosis","Known hypersensitivity to glyburide or sulfonamides","Concomitant use with bosentan"]