Metformin Flashcards
what flower does metformin come from?
french lilac, goats rue
what is the active component of French lilac?
guanidine
what is biguanide?
2 guanidine stuck together
what is the formulation of metformin?
dimethylbiguanide
what is metformin said to be?
weak cellular poison
how does metformin work?
inhibits complex 1 of the mitochondrial respiration chain (electoral transport chain)
what does the inhibition of the mitochondrial respiratory chain result in?
fall in cellular ATP (increase in ADP/ATP ratio), rise in AMP:ATP, activation of AMPK, reduction in gluconeogenesis (glucose production by liver)
what causes the reduction in gluconeogenesis?
could be mediated by rise in AMP kinase but probably secondary due to rise in AMP
what does the effects of metformin depend on?
where in the body it gets to
is metformin hydrophobic or hydrophilic?
hydrophilic
what does the hydrophilic nature of metformin mean?
it is not readily taken up by cells, only taken into cells that readily actively transport
what transporters does metformin require?
organic cation transporters (OCT’s)
what tissues is metformin present in?
intestines, liver and kidney (rarely gets into other tissues)
how is metformin excreted?
unchanged in the urine (metformin is not metabolised)
what is the main physiological mechanism of metformin?
lowers hepatic glucose production and increases gut glucose utilisation and metabolism
what is an additional mechanism of metformin?
increases intestinal GLP-1 secretion, alters gut microbiome, decreases lipogenesis, reduces inflammation
how potent is metformin?
one of the most potent drugs, lowers HbA1c by around 18mmol/mol
what is the weight loss possibility?
weight neutral or weight losing
what is the usual dose?
500mg bd
what is the max dose?
1g a day
which dosage is better tolerated?
once daily
how expensive is metformin?
cheap, £3.20 per month for 500mg bd
what are some side effects of metformin?
gi intolerance; diarrhoea, bloating, abdominal pain, dyspepsia, metallic taste in mouth
what do the gi symptoms reflect?
high concentration of metformin in the intestine (concentrated 500 fold in he enterocytes)
how to adjust dose in response to gi symptoms?
500g od for a week and increase by 500mg od per week or modified release formulation if can’t tolerate above
