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Glimepiride

Glimepiride, a third-generation sulfonylurea, is a widely used oral antidiabetic agent for managing type 2 diabetes mellitus (T2DM). Known for its potent glucose-lowering effects and once-daily dosing, it is often prescribed when lifestyle modifications and first-line therapies (e.g., metformin) fail to achieve glycemic control. This article integrates evidence from the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to detail its mechanism of action, clinical uses, dosing, side effects, precautions, drug interactions, and pharmaceutical nomenclature

Glimepiride lowers blood glucose through:

Pancreatic Beta-Cell Stimulation:

Binds to ATP-sensitive potassium (Kₐₜₚ) channels on pancreatic β-cells, closing the channels and depolarizing the cell membrane. This triggers calcium influx and insulin secretion (Lippincott).

Extrapancreatic Effects:

Enhances peripheral insulin sensitivity over time by increasing glucose uptake in muscle and adipose tissue (Lange).

BNF-Approved Indications:

Type 2 Diabetes Mellitus: Monotherapy or combined with other agents (e.g., metformin, insulin) when diet/exercise and first-line treatments are insufficient.

Contraindications:

Type 1 diabetes, diabetic ketoacidosis, severe renal/hepatic impairment (BNF).

Initial Dose: 1 mg once daily, taken with breakfast or the first main meal (BNF).

Maintenance: Titrate every 1–2 weeks based on glycemic response.

Maximum Dose: 4–6 mg daily (up to 8 mg under specialist supervision).

Renal/Hepatic Impairment:

Avoid in severe renal impairment (eGFR <30 mL/min/1.73m²) or hepatic failure due to hypoglycemia risk (BNF).

Hypoglycemia: Most frequent adverse effect, particularly in elderly or malnourished patients.

Weight Gain: Moderate (2–4 kg) due to insulin-mediated anabolism (Lippincott).

Gastrointestinal: Nausea, dizziness, headache.

Rare but Serious:

Hypersensitivity: Skin rashes, Stevens-Johnson syndrome.

Hematologic: Leukopenia, thrombocytopenia (BNF).

Contraindications:

Hypersensitivity to sulfonylureas, porphyria (BNF).

Regular blood glucose checks, HbA1c (target ≤7% for most adults).

Renal and hepatic function annually (Lange).

Contraindicated (BNF category not recommended; insulin preferred).

Hypoglycemia Risk Enhancers:

Beta-Blockers: Mask hypoglycemia symptoms (e.g., tachycardia, sweating).

Alcohol: Potentiates hypoglycemia and disulfiram-like reactions (BNF).

CYP2C9 Inhibitors:

Fluconazole, Warfarin: Increase glimepiride levels, raising hypoglycemia risk (Lippincott).

Hyperglycemia Inducers:

Corticosteroids, Thiazide Diuretics: Counteract glucose-lowering effects (Lange).

Generic Name: Glimepiride.

Brand Names:

UK (BNF): Amaryl®, Solosa®.

US: Amaryl®, others vary by manufacturer

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