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Section IVOther important drugsBiguanides
Metformin
Metformin is the only currently available biguanide in the UK.Mechanism of action
This is thought to include delayed uptake of glucose from the gut, increased periph-
eral insulin sensitivity (increasing peripheral glucose utilization) and inhibition of
hepatic and renal gluconeogenesis.Other effects
Gastrointestinal disturbances including diarrhoea sometimes occur but are gener-
ally mild. More significantly is its ability to precipitate severe lactic acidosis especially
if taken by alcohol abusers or in the presence of renal impairment. It also lowers
plasma cholesterol, triglycerides and low-density lipoproteins.Kinetics
Metformin is slowly absorbed from the gut with a bioavailability of 60%. It is not
bound by plasma proteins and is excreted unchanged in the urine. Renal impairment
significantly prolongs its actions.Other antidiabetics
Acarbose
Acarbose is a competitive inhibitor of intestinalα-glucosidase with a specific action
on sucrase. Polysaccharides are therefore not metabolized into their absorbable
monosaccharide form. This delay in intestinal glucose absorption reduces the post-
prandial hyperglycaemia normally seen in diabetics.
Itis not absorbed significantly and has few other systemic effects. Owing to an
increased carbohydrate load reaching the bacterial flora in the large bowel patients
may experience borborygmi, flatulence and diarrhoea. Hepatic transaminases may
be transiently raised.Thiazolidinediones
Rosiglitazone and pioglitazone
Thiazolidinediones are oral antidiabetic agents with a high oral bioavailability. There
effects may take weeks to be fully established due to their mechanism of action.
Troglitazone was withdrawn due to hepatitis and consequently patients taking thi-
azolidinediones require liver function monitoring.