Metformin

Class Oral hypoglycaemic
Chemistry

Biguanide

Routes of administration

Oral only

Absorption

Completely absorbed, oral bioavailability 40-60%

Solubility

pKa=12.4; good water solubility

Distribution

VOD= 1-4 L/kg; minimally protein bound

Metabolism

Minimal metabolism

Elimination

90% of the dose is cleared renally

Time course of action

Half life 6 hrs

Target receptor

Complex I of the mitochondrial respiratory chain (and, indirectly, AMPK)

Mechanism of action

By disabling the mitochondrial respiratory chain, biguanides decrease the ATP supply to hepatocytes, activating AMPK (a fuel-sensing enzyme which regulates the balance of anabolic and catabolic activity). The result is an activation of fatty acid oxidation and a deactivation of glycogenolysis and gluconeogenesis. Systemic glucose delivery from the liver is therefore decreased.

Clinical effects

Hypoglycaemia, but also:
- lactic acidosis
- diarrhoea
- abdominal discomfort
- anorexia
- taste disturbance

Literature reference

Rena et al, 2017

CICM details of understanding Level 3
Mentioned around Deranged Physiology
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