GLIMEPIRIDE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Glimepiride binds to sulfonylurea receptor (SUR1) on pancreatic beta cells, closing ATP-sensitive potassium channels, leading to membrane depolarization, calcium influx, and insulin secretion.

What the body does with it

Metabolism	Primarily metabolized by CYP2C9 to inactive metabolites (M1 and M2). Minor metabolism by CYP2C19.
Excretion	Approximately 60% renal excretion as metabolites (mainly M1 and M2) and 40% fecal/biliary elimination; <2% excreted unchanged.
Half-life	5–9 hours (terminal elimination half-life); clinically, dosing is once daily due to prolonged receptor binding and glucose-lowering effect.
Protein binding	>99.5% bound to albumin.
Volume of Distribution	Approximately 0.12 L/kg; low Vd indicates limited extravascular distribution.
Bioavailability	Oral: ~100%
Onset of Action	Oral: Peak insulin secretion occurs within 2–3 hours; glucose-lowering effect begins within 1–2 hours.
Duration of Action	Up to 24 hours; suitable for once-daily dosing, though may be extended in hepatic or renal impairment.

Classification & Brands

Dosing & administration

1-4 mg orally once daily, typically with breakfast; maximum dose 8 mg/day. Start at 1-2 mg/day and titrate by 1-2 mg every 1-2 weeks based on glycemic response.

Dosage form	TABLET
Renal impairment	eGFR 30-59 mL/min: start at 1 mg/day and titrate cautiously; eGFR <30 mL/min: contraindicated (increased risk of hypoglycemia).
Liver impairment	Child-Pugh Class A or B: start at 1 mg/day and titrate cautiously; Child-Pugh Class C: not recommended (lack of data and increased hypoglycemia risk).
Pediatric use	Not FDA-approved for pediatric use; limited data from clinical trials: 1-8 mg/day started at 1 mg, titrated in 1 mg increments every 2 weeks, but not recommended in guidelines.
Geriatric use	Start at 1 mg/day; avoid doses >6 mg/day due to increased hypoglycemia risk; monitor renal function; use cautiously with multiple medications.

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	Excreted in human milk; M/P ratio not established. Potential for hypoglycemia in breastfed infant. Manufacturer advises caution; consider alternative agents or monitor infant blood glucose.
Teratogenic Risk	Pregnancy Category C. First trimester: Limited data; potential risk of hypoglycemia-related malformations. Second and third trimesters: May cause neonatal hypoglycemia and macrosomia. Avoid use in pregnancy; switch to insulin.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Increased risk of cardiovascular mortality based on findings from the University Group Diabetes Program (UGDP) study with tolbutamide, a similar drug. However, this warning may not be specific to glimepiride and is included in labeling for all sulfonylureas.

Side Effect Profile

Common Effects	Hypoglycemia
Serious Effects

Absolute Contraindications

["Type 1 diabetes mellitus","Diabetic ketoacidosis (with or without coma)","Known hypersensitivity to glimepiride or any sulfonylurea","Severe renal or hepatic impairment"]

Clinical Precautions

Precautions

["Hypoglycemia, especially in elderly, debilitated, or patients with renal/hepatic impairment","Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency","Potential for increased cardiovascular mortality (see black box warning)","Hepatic effects: liver enzyme elevations, rare cholestatic jaundice"]

Clinical Tips & Counseling

Drug interactions

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