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Drugs, Supplies and Delivery
Metformin
Metformin, a cornerstone in the management of type 2 diabetes mellitus (T2DM), is renowned for its efficacy, safety, and pleiotropic benefits. This article synthesizes evidence from the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to provide a detailed overview of its mechanism of action, clinical uses, dosing, side effects, precautions, and drug interactions
Metformin, a biguanide, exerts its antihyperglycemic effects through multiple pathways:
Hepatic Gluconeogenesis Inhibition
Activates AMP-activated protein kinase (AMPK), a cellular energy sensor, reducing hepatic glucose production (Lippincott).
Suppresses mitochondrial glycerophosphate dehydrogenase, altering redox potential and inhibiting gluconeogenesis (Lange).
Peripheral Insulin Sensitivity:
Enhances glucose uptake in skeletal muscle and adipose tissue by improving insulin receptor tyrosine kinase activity (Lange).
Gastrointestinal Effects:
Modulates gut microbiota, increasing glucagon-like peptide-1 (GLP-1) secretion, which suppresses appetite and improves glucose regulation (emerging research noted in Lippincott).
Primary Indication:
Type 2 Diabetes Mellitus: First-line therapy, particularly for overweight patients (BNF). Often combined with lifestyle modifications or other agents (e.g., sulfonylureas, SGLT2 inhibitors).
Off-Label Uses:
Polycystic Ovary Syndrome (PCOS): Improves insulin resistance and regulates menstrual cycles (Lange).
Prediabetes: Reduces progression to T2DM (Lippincott).
Initial Dose: 500 mg once daily (with meals) to minimize gastrointestinal (GI) effects (BNF).
Maintenance: Titrate weekly by 500 mg, up to 2,000–3,000 mg/day in divided doses.
Extended-Release (XR): 500–2,000 mg once daily (BNF).
Renal Adjustment:
Avoid if eGFR <30 mL/min/1.73m².
Use with caution if eGFR 30–45 mL/min/1.73m² (BNF).
Common:
GI disturbances (30% of patients): Nausea, diarrhea, abdominal pain (Lippincott).
Rare but Serious:
Lactic Acidosis: Risk factors include renal/hepatic impairment, alcoholism, and acute hypoxia (BNF).
Vitamin B12 Deficiency: Long-term use may impair absorption; monitor levels annually (Lange).
Contraindications:
Severe renal impairment (eGFR <30), metabolic acidosis, acute dehydration (BNF).
Elderly: Higher risk of renal dysfunction; monitor eGFR regularly.
Pregnancy: Category not recommended; use only if benefits outweigh risks (BNF).
Cimetidine: Competes for renal tubular secretion, increasing metformin levels (BNF).
Alcohol: Potentiates lactate production; avoid excessive intake (Lange).
Loop Diuretics: May worsen renal function, increasing lactic acidosis risk (Lippincott).
Insulin/Sulfonylureas: Enhanced hypoglycemia risk when combined (BNF).
Generic: Metformin hydrochloride.
Brand Names: Glucophage®, Glumetza®, Fortamet®, Riomet® (liquid formulation).
