Metformin is a biguanide with antihyperglycaemic effects,
lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Metformin may act via 3 mechanisms: Reduction of hepatic glucose production by
inhibiting gluconeogenesis and glycogenolysis; in muscle by increasing insulin sensitivity,
improving peripheral glucose uptake and utilisation; and delay of intestinal glucose absorption.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase.
Metformin increases the transport capacity of all types of membrane glucose transporters (GLUT).
In humans, independently of its action on glycaemia, metformin has favourable effects on lipid metabolism.
This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies;
metformin reduces total cholesterol, LDL cholesterol and triglyceride levels.
After an oral dose of metformin,
Tmax is reached in 2.5 hours. Absolute bioavailability of a 500mg or 850mg metformin
tablet is approximately 50-60% in healthy subjects. Metformin is excreted unchanged
in the urine. No metabolites have been identified in humans.
It is used in the treatment of maturity
on-set diabetes mellitus not responsive to diet alone or diet plus treatment with a sulphonylurea.
Side effects/Adverse reactions
Anorexia, nausea, vomiting and diarrhoea,
are not uncommon; occasionally a metallic taste, loss of weight, weakness, lassitude or skin rashes may occur.
Lactic acidosis possibly heralded by vomiting, abdominal pain, hyperventilation and diminished consciousness may occur.
Metformin hydrochloride should not be
given to patients with impaired hepatic or renal function, cardiovascular collapse,
congestive heart failure, acute myocardial infarction, or other conditions leading
to hypotension or to hypoxaemia. It should not be given to patients with diabetes
mellitus complicated by acidosis, infection or gangrene or during pregnancy or during surgery.
Warnings and Precautions
Lactic acidosis is rare, but serious
(high mortality in the absence of prompt treatment) metabolic complication that can
occur due to metformin accumulation during treatment with metformin. Reported cases
of lactic acidosis in patients on metformin have occurred primarily in diabetic patients
with significant renal failure. The incidence of lactic acidosis can and should be
reduced by assessing also other associated risk factors such as poorly controlled diabetes,
ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia.
As metformin is excreted by the kidney,
serum creatinine levels should be determined before initiating treatment and regularly monitored.
Decreased renal function in elderly subjects is frequent and asymptomatic.
Special caution should be exercised in situations where renal function may become
impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with NSAID.
Administration of iodinated contrast agent
As the intravascular administration of
iodinated contrast materials in radiologic studies can lead to renal failure, metformin
should be discontinued prior to, or at the time of the test and not reinstituted until
48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
Metformin hydrochloride should be discontinued
48 hours before elective surgery with general anaesthesia and should not be usually resumed earlier than 48 hours afterwards.