GLYBURIDE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Glyburide stimulates insulin secretion from pancreatic beta cells by binding to the sulfonylurea receptor (SUR1) and blocking ATP-sensitive potassium channels, leading to cell depolarization and calcium influx.

What the body does with it

Metabolism	Hepatic metabolism via CYP2C9 to several metabolites, including 4-trans-hydroxyglyburide and 3-cis-hydroxyglyburide, which have minimal hypoglycemic activity.
Excretion	Renal (50% as metabolites, <5% unchanged); fecal (50% via bile).
Half-life	Terminal elimination half-life: 10 hours (range 5-16 hours). In renal impairment, half-life prolonged; clinical relevance: drug accumulation risk.
Protein binding	99% bound to albumin.
Volume of Distribution	0.3 L/kg (approximately 20 L in 70 kg adult). Indicates distribution mainly in extracellular fluid.
Bioavailability	Oral: 100% (well absorbed).
Onset of Action	Oral: 1-1.5 hours (peak serum concentrations); glucose-lowering effect begins within 1-2 hours.
Duration of Action	Duration: 12-24 hours (up to 24 hours). Clinical note: once-daily dosing; risk of prolonged hypoglycemia in elderly or renal impairment.

Classification & Brands

Dosing & administration

1.25-20 mg orally per day, divided into 1-2 doses; initial dose 2.5-5 mg/day, titrate every 1-2 weeks.

Dosage form	TABLET
Renal impairment	eGFR ≥60 mL/min: no adjustment; eGFR 30-59: start with 1.25 mg/day, titrate cautiously; eGFR <30: contraindicated.
Liver impairment	Child-Pugh A: no data; Child-Pugh B/C: contraindicated due to risk of hypoglycemia.
Pediatric use	Not recommended; safety and efficacy not established in pediatric patients.
Geriatric use	Start with 1.25 mg/day due to increased risk of hypoglycemia; monitor closely.

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.

Breastfeeding

Glyburide is excreted into breast milk in low concentrations; estimated relative infant dose is <1% of weight-adjusted maternal dose. M/P ratio is approximately 0.4–0.6. No adverse effects have been reported in nursing infants. Considered compatible with breastfeeding by the American Academy of Pediatrics; however, monitor infant for hypoglycemia symptoms.

Teratogenic Risk

Glyburide is classified as FDA Pregnancy Category C. In first trimester, human data do not indicate increased risk of major malformations; however, animal studies have shown fetal harm at high doses. In second and third trimesters, use may be associated with neonatal hypoglycemia and macrosomia due to maternal glycemic control. Risk of perinatal mortality and congenital anomalies is increased with poorly controlled diabetes, which outweighs potential drug risks.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Common Effects	Hypoglycemia
Serious Effects

Absolute Contraindications

["Type 1 diabetes mellitus","Diabetic ketoacidosis","Severe renal impairment (eGFR <30 mL/min/1.73 m²)","Hypersensitivity to glyburide or sulfonylureas","Concomitant use with bosentan"]

Clinical Precautions

Precautions

["Hypoglycemia: Risk increased with renal impairment, elderly, debilitated patients, or use with other antidiabetic agents.","Cardiovascular mortality: Possible increased risk compared to diet or diet plus insulin (UKPDS study).","Hemolytic anemia: Patients with G6PD deficiency.","Hepatic impairment: May prolong half-life and increase hypoglycemia risk.","Renal impairment: Contraindicated in severe renal disease."]

Clinical Tips & Counseling

Drug interactions

Loading safety data…