Metformin is a first-line oral biguanide antihyperglycemic agent, widely prescribed for the management of type 2 diabetes mellitus (T2DM) in India. It is the cornerstone of therapy due to its efficacy, safety profile, low cost, and cardiovascular benefits. It primarily works by decreasing hepatic glucose production (gluconeogenesis), increasing peripheral insulin sensitivity, and modestly delaying intestinal glucose absorption. Unlike sulfonylureas, it does not stimulate insulin secretion and carries a very low risk of hypoglycemia when used as monotherapy.
Adult: Initial dose: 500 mg once or twice daily with meals. Usual maintenance dose: 500 mg three times daily or 850 mg twice daily. Maximum effective dose is often 2000 mg/day, administered in divided doses.
Note: Take with or immediately after meals to minimize gastrointestinal side effects. Swallow the tablet whole with a glass of water. Do not crush or chew. For twice-daily dosing, take with breakfast and dinner.
Metformin's primary mechanism is the activation of AMP-activated protein kinase (AMPK), a key cellular energy sensor. This activation occurs both directly and indirectly via inhibition of mitochondrial complex I, leading to a decrease in hepatic gluconeogenesis and an increase in peripheral glucose uptake and utilization. It also improves insulin sensitivity by enhancing insulin receptor tyrosine kinase activity.
Pregnancy: Pregnancy Category B (US FDA). Not the drug of choice for gestational diabetes (insulin is preferred). May be used if benefits outweigh risks. Should be discontinued before planned pregnancy or as soon as pregnancy is confirmed, switching to insulin.
Driving: Metformin alone does not cause hypoglycemia and typically does not impair driving. However, patients on combination therapy with insulin or sulfonylureas should be cautious.
| Iodinated Contrast Media | Increased risk of lactic acidosis and acute renal failure. Metformin must be withheld. | Major |
| Cimetidine | Increases metformin plasma levels by reducing renal tubular secretion. | Moderate |
| Furosemide & Other Loop Diuretics | May alter renal function and increase metformin levels; also potential hyperglycemia. | Moderate |
| Beta-blockers (e.g., Propranolol) | May mask hypoglycemic symptoms and potentially cause hyperglycemia. | Moderate |
| Alcohol | Potentiates metformin's effect on lactate metabolism; increases risk of lactic acidosis and hypoglycemia. | Major |
| Corticosteroids (e.g., Prednisolone) | Antagonize hypoglycemic effect, leading to loss of glycemic control. | Moderate |
| Topiramate | May increase risk of lactic acidosis. | Moderate |