Pharmacological Classification
Class: Biguanide.
Action: Oral antihyperglycemic agent.
Chemical Identity: White crystalline compound

Clinical Indications

• Type 2 Diabetes Mellitus: The primary first-line treatment for adults and pediatric patients (10+ years) as an adjunct to diet and exercise.
• Gestational Diabetes: Frequently used to manage blood sugar during pregnancy.
• Prediabetes Management: Recommended for high-risk individuals (BMI >35, age 25–59) to prevent or delay the onset of type 2 diabetes.
• New 2026 Guidelines: Recent updates suggest considering metformin for preventing hyperglycemia in patients treated with specific cancer drugs (PI3Kα inhibitors) or high-dose glucocorticoids.
• Off-label Uses: Commonly used for Polycystic Ovary Syndrome (PCOS) to improve insulin sensitivity and ovulation.

Mechanism of Action

• Hepatic Suppression: Primarily works by inhibiting gluconeogenesis (glucose production) in the liver.
• Peripheral Sensitivity: Increases glucose uptake and utilization in skeletal muscles and adipose tissue.
• Intestinal Modulation: Slows the absorption of glucose in the gut and increases the secretion of GLP-1 (incretin).
• Mitochondrial Target: Inhibits mitochondrial complex I, which increases the AMP:ATP ratio, activating the energy-sensing enzyme AMPK.

Key Safety & Precautions

• Lactic Acidosis (Black Box Warning): A rare but life-threatening complication characterized by a buildup of lactic acid. Risk factors include severe renal impairment, congestive heart failure, and excessive alcohol consumption.
• Renal Thresholds: Contraindicated if eGFR is below 30 mL/min/1.73 m2. Dosage adjustment is required for patients with moderate renal impairment (eGFR 30–59).
• Nutritional Impact: Long-term use is associated with Vitamin B12 deficiency, requiring periodic screening.
• Gastrointestinal Distress: Most common side effects include nausea, diarrhea, and abdominal pain, often mitigated by using extended-release (ER) formulations or taking the drug with meals.