glipizide
Brand: Glucotrol, Glucotrol XL
ISMP High Alert Beers Criteria Prototype Drug
Drug Class: antidiabetic
Drug Family: antidiabetic
Subclass: sulfonylurea / second-generation
Organ Systems: endocrine
Mechanism of Action
Binds and closes K-ATP channels on pancreatic beta cells, causing membrane depolarization; voltage-gated calcium channels open, calcium influx triggers exocytosis of insulin-containing granules; stimulates insulin secretion independent of blood glucose — mechanism underlying hypoglycemia risk.
ATP-sensitive potassium channels (K-ATP) on pancreatic beta cells
Indications
- type 2 diabetes mellitus (monotherapy or combination)
Contraindications
- type 1 diabetes mellitus
- diabetic ketoacidosis
Adverse Effects
Common
- hypoglycemia (most significant — can be severe and prolonged)
- weight gain
- nausea
- epigastric discomfort
Serious
- severe hypoglycemia (especially in elderly, renal impairment, irregular meal schedule)
- hemolytic anemia (cross-reactivity with sulfonamide allergy)
- hepatotoxicity (rare)
- SIADH/hyponatremia
Pharmacokinetics (ADME)
| Absorption | ~100% oral; take 30 minutes before meals |
| Distribution | Protein binding >98%; Vd ~0.2 L/kg; does not cross BBB |
| Metabolism | CYP2C9 to inactive metabolites |
| Excretion | Renal (~68%) and fecal; shorter half-life and inactive metabolites make glipizide preferred over glyburide in elderly |
| Half-life | 2–4 hours (IR); 24 hours (XL due to delivery system) |
| Onset | 30 minutes |
| Peak | 1–3 hours |
| Duration | 12–24 hours |
| Protein Binding | >98% |
| Vd | ~0.2 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| fluconazole / miconazole | CYP2C9 inhibition increases glipizide levels; severe hypoglycemia risk | major |
| beta-blockers | mask tachycardia hypoglycemia warning; non-selective agents also impair glycogen release | moderate |
| NSAIDs / sulfonamides / fibrates | displace from protein binding or enhance hypoglycemic effect | moderate |
Nursing Considerations
- Administer 30 minutes before first meal of the day; skipping a meal after taking sulfonylurea is a major hypoglycemia risk — counsel patients about consistent meal timing
- Preferred sulfonylurea in elderly and CKD patients (compared to glyburide, which has active metabolites that accumulate in renal failure) — however, all sulfonylureas should be used with caution in the elderly
- Monitor blood glucose closely when adding or removing CYP2C9 inhibitors/inducers; dose adjustment frequently required
- For severe hypoglycemia: IV dextrose (D50W) 25 mL bolus followed by D10W infusion; monitor glucose q30 min; prolonged hypoglycemia from sulfonylureas may require octreotide
Clinical Pearls
- Sulfonylurea hypoglycemia is more dangerous than insulin hypoglycemia in terms of duration — the long-acting nature of K-ATP channel closure and continued insulin release means hypoglycemia can recur after initial glucose treatment without a continuous glucose infusion
- Among sulfonylureas, glipizide is preferred over glyburide in elderly patients because glyburide is metabolized to active metabolites that accumulate with renal dysfunction, dramatically increasing hypoglycemia risk
Safety Profile
Pregnancy safe
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.