Generic Name

Glucotrol

Mechanism

• Selective inhibition of pancreatic β‑cell K⁺⁺‑ATP channels → depolarization → calcium influx → insulin release.
• Stimulates insulin secretion independent of glucose levels, leading to hypoglycemia risk if not matched with diet/exercise.
• Adds to the effect of other glucose‑lowering agents, enhancing glycemic control.

Pharmacokinetics

• Absorption: Rapid, peak plasma concentration 0.5–3 h after oral dosing. 70–80 % bioavailability.
• Distribution: Broad tissue penetration; high protein binding (~90 %).
• Metabolism: Hepatic via CYP2C8 and CYP3A4 → active metabolites.
• Elimination: 85 % excreted renally (both unchanged drug and metabolites).
• Half‑life: 4–6 h; therapeutic effect persists >24 h due to sustained insulin release.

Indications

• Type 2 diabetes mellitus as monotherapy, add‑on, or basal‑bolus insulin combination.
• Combination therapy with metformin, thiazolidinediones, or GLP‑1 receptor agonists for additional glycemic control.

Contraindications

• Contraindications:
• Type 1 diabetes (risk of severe hypoglycemia).
• Diabetic ketoacidosis.
• Hypersensitivity to sulfonylureas or any excipients.
• Warnings:
• Cognitive impairment, renal or hepatic dysfunction → dose adjustment.
• Pregnancy: Category D; contraindicated.
• Concurrent use with quinolones or CYP3A4 inhibitors may increase hypoglycemia risk.

Dosing

• Initial dose: 5 mg once daily (≤70 kg) or 2.5 mg (≥70 kg).
• Maintenance: 10–40 mg/day, titrated in increments of 5–10 mg every 2–4 weeks based on fasting plasma glucose or A1C.
• Administration: Oral tablets with or without food; split dose (below‑meal and morning‑meal) for tighter control.
• Renal impairment: Reduce maximum daily dose to 40 mg or less; avoid in CrCl <30 mL/min.
• Over‑dosage: Treat with dextrose or intravenous glucose; insulin may be required.

Adverse Effects

• Common:
• Hypoglycemia (most frequent).
• Weight gain.
• Nausea, headache, dizziness.
• Serious:
• Severe hypoglycemia (altered consciousness, seizures).
• Hypersensitivity reactions (rash, angioedema).
• Liver injury (rare elevations in ALT/AST).
• Rare:
• Pancreatitis, heart failure exacerbation.

Monitoring

• Baseline & follow‑up A1C every 3–6 months; fasting glucose 1–2 weeks after titration.
• Renal function (Serum creatinine/CrCl) at baseline, then annually (or sooner if dose change).
• Liver enzymes if symptoms of hepatotoxicity.
• Signs of hypoglycemia; educate patients/tools for glucose monitoring.

Clinical Pearls

• Steep Decline Rule: Small dosing changes dramatically affect hypoglycemia risk; adjust by ≤5 mg stepwise.
• Meal‑Timing Strategy: To reduce hypoglycemia, give drug 1 h before a satiety meal rather than at bedtime.
• Tailoring for Renal Impairment: In CKD patients, start at 2.5 mg and prohibit above 40 mg/d; consider sulfonylureas with little renal excretion (e.g., gliclazide).
• Combination with Metformin: Target an A1C <7 % with *Glucotrol* + metformin avoids weight gain seen with insulin or sulfonylurea monotherapy.
• Hypoglycemia‑Unfriendly States: In patients prone to hypoglycemia (elderly, heart failure, kidney disease), monitor frequent glucose checks; patient diaries help titrate safely.

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• Keywords: Glucotrol, glipizide, sulfonylurea, type 2 diabetes, hypoglycemia, renal dose adjustment, pharmacokinetics, clinical monitoring.