Generic Name

Glipizide

Mechanism

Glipizide is a second‑generation sulfonylurea that stimulates insulin release from pancreatic β‑cells.
• Binds the sulfonylurea receptor 1 (SUR1) subunit of the ATP‑sensitive potassium (*KATP*) channel on β‑cell membranes.
• Inhibition of the *KATP* channel closes voltage‑gated potassium channels, causing depolarization.
• Depolarization opens voltage‑gated calcium channels → influx of Ca²⁺.
• Calcium‑mediated exocytosis of insulin granules increases circulating insulin regardless of blood glucose level, improving glycemic control.

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Pharmacokinetics

• Absorption: Oral tablets are rapidly absorbed; bioavailability ≈ 70‑80 %.
• Peak plasma concentration (Tmax): ~ 2–3 h post‑dose.
• Half‑life: 3–5 h (short‑acting profile).
• Protein binding: ~ 81 % (albumin).
• Metabolism: Primarily hepatic via CYP2C9 to inactive metabolites.
• Excretion: Renal (≈ 70 % of metabolites) and fecal.
• Renal impairment: Metabolites accumulate; dose adjustment required (see section below).

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Indications

• Type 2 diabetes mellitus (T2DM) – adjunct to diet and exercise; used alone or with metformin, TZDs, or insulin.
• Not indicated for type 1 DM, gestational diabetes (glyburide preferred), or pancreatitis.

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Contraindications

• Contraindicated
• Type 1 diabetes
• Sulfonylurea or sulfa allergy
• Severe hepatic impairment (ALT > 3× ULN)
• Warnings
• Hypoglycemia: higher risk with skipped meals, excessive alcohol, or prolonged fasting.
• Renal impairment: prolonged half‑life of metabolites → hypoglycemia risk.
• Pregnancy/Lactation: category B; breastfeeding discouraged.
• Elderly: increased sensitivity; start low.

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Dosing

• Administration tips
• Take with a meal to minimize hypoglycemia.
• Consistent timing each day.
• In patients on chronic steroids or those with high–protein diets, monitor glucose closely.

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Adverse Effects

• Common (≥ 5 %)
• Hypoglycemia (most frequent)
• Nausea, vomiting, abdominal discomfort
• Headache, dizziness
• Rash, pruritus
• Serious (≤ 1 %)
• Severe hypoglycemia → seizures, loss of consciousness
• Allergic reactions (anaphylaxis, angioedema)
• Hepatotoxicity (↑ ALT/AST)
• Acute pancreatitis
• Fluid retention / worsening heart failure

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Monitoring

• Blood glucose: Self‑monitoring fasting & post‑prandial; adjust dose accordingly.
• HbA1c: Every 3 months (or as per guidelines).
• Renal function: Serum creatinine & eGFR at baseline, then every 6 months.
• Liver enzymes: ALT/AST at baseline, 1 month after initiating therapy, then annually.
• Weight & BMI: Monitor for unintended weight gain.
• Signs of hypoglycemia: Document episodes and adjust therapy.

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Clinical Pearls

• Short‑acting advantage: Glipizide’s 3–5 h half‑life limits nocturnal hypoglycemia compared with long‑acting agents.
• Start low, go slow: Elderly and those with renal disease should begin at the lowest dose and titrate by 1–2 weeks, not daily, to avoid rebound hypoglycemia.
• Meal timing is key: Administering at breakfast or a main meal optimally times insulin surge with carbohydrate intake.
• Avoid concurrent sulfonylurea‑like integrators (e.g., otherized drugs) that may increase hypoglycemia risk.
• Discontinue in severe hepatic dysfunction: Because hepatic metabolism is essential for inactivation, accumulation can precipitate toxicity.
• Emergency hypoglycemia kit: Keep glucose tablets or gel on hand; treat promptly at < 70 mg/dL and consider dextrose 25 g if unconscious.
• Drug interactions matter: Cimetidine, fluconazole, and other CYP2C9 inhibitors can raise glipizide levels, augmenting hypoglycemia risk.
• Pregnancy caution: While category B, data are limited; if pregnancy is confirmed, consider switching to a safer oral agent (e.g., metformin).
• Monitoring for pancreatitis: New epigastric pain with elevated lipase warrants discontinuation and evaluation.

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• Keywords: Glipizide, sulfonylurea, short‑acting insulin secretagogue, type 2 diabetes therapy, hypoglycemia risk, renal impairment dosing, metabolic monitoring, pharmacokinetics.