Metformin
Overview
Metformin is a first-line oral antidiabetic medication widely used to treat type 2 diabetes mellitus. It effectively lowers blood sugar levels and improves insulin sensitivity without typically causing weight gain or significant hypoglycaemia (low blood sugar) when used alone.
Mechanism of Action
It belongs to the biguanide class of medications. Its primary mechanism of action is decreasing hepatic glucose production (gluconeogenesis). Additionally, it decreases intestinal absorption of glucose and improves peripheral tissue sensitivity to insulin, thereby increasing cellular glucose uptake and utilisation. It does not stimulate insulin secretion, which explains its low risk of causing hypoglycaemia.
Dosage and Administration
The starting dose is usually 500 mg once or twice daily, taken with meals to minimise gastrointestinal side effects. The dose is gradually titrated up over weeks based on blood glucose control, up to a maximum recommended daily dose of 2000 mg to 2550 mg (depending on the formulation). Extended-release versions are typically taken once daily with the evening meal.
Side Effects
The most common side effects are gastrointestinal, including nausea, vomiting, diarrhoea, abdominal pain, and loss of appetite. These often subside over time or with a slower dose titration. Long-term use can lead to vitamin B12 deficiency. A rare but serious complication is lactic acidosis, characterised by muscle pain, breathing difficulties, and lethargy.
Contraindications
It is strictly contraindicated in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²), acute or chronic metabolic acidosis (including diabetic ketoacidosis), and conditions that may lead to tissue hypoxia (such as acute heart failure or severe infection) due to the increased risk of lactic acidosis.
Pregnancy and Lactation
Metformin is sometimes used during pregnancy to manage gestational diabetes or pre-existing type 2 diabetes, though insulin is traditionally preferred. It is excreted in human milk in small amounts, but is generally considered compatible with breastfeeding.
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