Dose 500-850mg 2G daily in divided doses with meals
, no therapeutic benefit of larger
doses, however max dose 3G
Daily.
Start 500mg- 850mg OD
with main meal and
slowly titrate dose to
avoid GI side effects.
Type 2 Diabetes Monotherapy 1st line NICE. Dual therapy
with sulphonylurea and or insulin.
Increased BMI
Cardioprotective
Contraindicated in Acute LVF ~ Increased risk of lactic acidosis
Stop post MI, restart after 2 weeks if LVF stable and renal function OK.
Lactic acidosis ~ Rarely
occurs except in extreme
illness and tissue hypoxia
acts as a trigger.
Impaired renal
function.
Tissue
hypoxia/MI/Sepsis.
Withdraw for 48 hours post contrast
media and restart only when renal
function OK.
Stop prior to planned
surgery/General Anaesthesia and
restart once eating and renal
function OK
Increased risk with
acute alcohol
intoxication
Pharmacokinetics
Oral bioavailability 50-60%
Steady state after 24- 48 hrs
Hydrophyllic
Not metabolised, cleared by tubular secretion.
Half life = 6.2 hours
No hypoglycaemia except in use with other OHAs
Caution with poor renal function,
Review if Creatinine>130 or
GFR<45. Not if creatinine >150.
When renal function impaired, renal clearance is decreased in
proportion to creatinine and therefore elimination half life is prolonged
leading to increased levels of metformin in plasma~ potential increase
risk of lactic acidosis
Pharmacology
Unclear mechanism of action.
Potential mechanism =Disruption of respiratory chain oxidation in
mitochondria and activation of enzyme - Adenosine
Monophosphate(AMP) to Activated Protein Kinase (AMPK).Activation of
AMPK stimulates Adenosine Triphosphate (ATP) involved with
maintenance of cellular energy stores.
In skeletal muscle AMPK
activation increases
glucose uptake and lipid
oxidation.
In the liver AMPK activation inhibits
gluconeogenesis and lipid synthesis but
increases lipid oxidation.
In Adipose tissue
AMPK activation
reduces lipolysis and
lipogenesis
Therefore activation of AMPK in skeletal muscle, liver and
adipose tissue results in decreased circulating glucose, lipids and
ectopic fat collection, as well as increased insulin sensitivity.
Increased insulin binding to
insulin receptors therefore
increased uptake of glucose
Biguanide
Interactions~ H2 receptor antagonist cimetidine, increased plasma concentration of
metformin by reducing clearance by the kidneys, both cleared by tubular secretion and
compete for the same transport mechanism.
First available in BNF in 1958, FDA approval in 1994
Pregnancy NICE Guidance, safe and effective in pregnancy