Metformin
Metformin is an oral biguanide and first-line pharmacological treatment for type 2 diabetes. It lowers hepatic glucose production and improves peripheral insulin sensitivity, with a long record of clinical experience.
- Chemical formula
- C4H11N5
- CAS number
- 657-24-9
- ATC code
- A10BA02
- Molecular weight
- 129.16 g/mol
- Drug class
- Biguanide
- Also known as
- Dimethylbiguanide, Metformina
What is it?
Metformin is a small-molecule biguanide derived from galegine, an alkaloid from Galega officinalis investigated since the 1920s. Approved in the United Kingdom in 1958 and in the United States in 1995, it is now the most widely prescribed oral antidiabetic in the world. Metformin appears on essential medicines lists of the World Health Organization and is available as immediate-release and extended-release tablets and as fixed-dose combinations with several other antidiabetic agents.
Mechanism of action
Metformin's principal effect is to suppress hepatic glucose production by inhibiting mitochondrial complex I, which raises the cellular AMP/ATP ratio and activates AMP-activated protein kinase. Secondary actions include modest improvement in peripheral insulin sensitivity and changes in gut microbiota and bile-acid signalling that may contribute to its glycaemic effect. The drug does not stimulate insulin secretion, which explains its low intrinsic risk of hypoglycaemia. Effects on weight are typically neutral or slightly favourable.
Pharmacokinetics
Metformin is absorbed in the small intestine, with absolute bioavailability of about 50% to 60% in fasted conditions. Plasma protein binding is negligible, and the drug is excreted unchanged by the kidneys via tubular secretion. The terminal half-life is approximately five hours for the immediate-release formulation. Renal impairment substantially reduces clearance and increases plasma concentrations, which is why eGFR-based dose adjustment and contraindications are described in the prescribing information.
Indications
Metformin is indicated as first-line oral therapy in adults and selected paediatric populations with type 2 diabetes mellitus, alone or in combination with other antidiabetic agents, including insulin. Off-label or label-extension uses in some markets include polycystic ovary syndrome, prediabetes and gestational diabetes under specialist supervision. According to international guidelines, metformin should be considered at diagnosis in most adults with type 2 diabetes unless contraindicated.
Safety profile
The most common adverse effects are gastrointestinal: nausea, diarrhoea, abdominal discomfort and metallic taste, often improved by gradual titration, food intake or use of the extended-release formulation. Vitamin B12 deficiency may develop with long-term use. The most serious but rare adverse event is lactic acidosis, almost exclusively seen in patients with significant renal impairment, severe heart failure, sepsis or hypoxia. According to the prescribing information, metformin is contraindicated below specific eGFR thresholds and should be temporarily withheld for iodinated contrast or surgery.
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Frequently asked questions
Why is metformin considered first-line therapy for type 2 diabetes? ▾
International guidelines recommend metformin at diagnosis in most adults with type 2 diabetes because of its favourable balance of efficacy, safety, tolerability and cost. It produces meaningful HbA1c reduction without intrinsic hypoglycaemia risk, is weight-neutral and has a long record of clinical use. Metformin can be combined with most other antidiabetic agents, which makes it a flexible backbone for treatment intensification.
Does metformin cause low blood sugar? ▾
Metformin does not stimulate insulin secretion, so when used alone it carries a very low intrinsic risk of hypoglycaemia. Hypoglycaemia can still occur in patients also receiving insulin or sulfonylureas, particularly during fasting, prolonged exercise or alcohol intake. According to the prescribing information, dose adjustment of insulin or secretagogues may be required when metformin is added or removed, under medical supervision.
Is the extended-release version different from the standard one? ▾
The extended-release tablet contains the same active molecule as the immediate-release form but is designed to release metformin over several hours. This often improves gastrointestinal tolerance, allows once-daily dosing and may reduce treatment discontinuation. Glycaemic efficacy is broadly comparable when total daily doses are equivalent. The choice between formulations is made by the prescriber based on tolerability and adherence considerations.
Is metformin safe long-term? ▾
Metformin has been used clinically for decades and has an extensive safety record. Long-term use can lower vitamin B12 levels in some patients, so periodic monitoring is recommended, especially in the elderly or those with peripheral neuropathy. According to clinical guidelines, patients should also have periodic renal function assessment because dose adjustments and contraindications depend on glomerular filtration rate.
What are the main contraindications for metformin? ▾
Metformin is contraindicated in severe renal impairment below specific eGFR thresholds defined in local labelling, in acute or chronic conditions that may cause tissue hypoxia such as decompensated heart failure, in hepatic failure, in acute alcohol intoxication and in known hypersensitivity to the molecule. According to the prescribing information, treatment should be temporarily interrupted around iodinated contrast administration and major surgery.
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