glyburide

Brand: DiaBeta, Micronase, Glynase

ISMP High Alert Beers Criteria Prototype: glipizide
Drug Class: sulfonylurea
Drug Family: antidiabetic
Subclass: second-generation sulfonylurea
Organ Systems: endocrine

Mechanism of Action

Binds to the SUR1 subunit of ATP-sensitive potassium channels on pancreatic beta cells, causing channel closure, membrane depolarization, calcium influx, and insulin secretion independent of glucose levels. Risk of hypoglycemia is highest among sulfonylureas due to its longest duration.

SUR1 subunit of ATP-sensitive K+ channels (pancreatic beta cells)

Indications

  • type 2 diabetes mellitus

Contraindications

  • type 1 diabetes
  • diabetic ketoacidosis
  • sulfonamide allergy
  • severe renal or hepatic impairment

Adverse Effects

Common

  • hypoglycemia (most common and most severe among sulfonylureas)
  • weight gain
  • nausea

Serious

  • severe prolonged hypoglycemia (especially in elderly)
  • cholestatic jaundice (rare)
  • agranulocytosis (rare)

Pharmacokinetics (ADME)

Absorption rapidly absorbed; bioavailability ~100%
Distribution highly protein bound (99%)
Metabolism hepatic via CYP2C9 to active metabolites
Excretion biliary/fecal (50%) and renal (50%)
Half-life 10 hours
Onset 15–30 minutes
Peak 1–4 hours
Duration 12–24 hours
Protein Binding 99%
Vd 0.12–0.14 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
fluconazole CYP2C9 inhibition increases glyburide levels, enhancing hypoglycemia risk major
NSAIDs displace from protein binding; additive hypoglycemia moderate
alcohol disulfiram-like reaction (flushing) and enhanced hypoglycemia moderate

Nursing Considerations

  1. Administer with breakfast or first main meal of the day to reduce hypoglycemia risk.
  2. Do not use in patients >65 years (Beers Criteria); prolonged hypoglycemia is especially dangerous in elderly due to blunted adrenergic response.
  3. Monitor fasting and postprandial glucose levels; hold glyburide and notify prescriber if patient is NPO for procedures.
  4. Educate patients about hypoglycemia recognition: shakiness, sweating, confusion, tachycardia; always carry fast-acting carbohydrate source.

Clinical Pearls

  • Glyburide is the sulfonylurea with the highest hypoglycemia risk due to its active metabolites and longest duration of action; glipizide or glimepiride are preferred in elderly patients.
  • Glyburide has a disulfiram-like interaction with alcohol, producing flushing, nausea, and tachycardia; advise patients to limit alcohol consumption.

Safety Profile

Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.