[e-drug] Metformin and Lactic acidosis (4)

["Leo Offerhaus" <offerhausl@euronet.nl>]

E-DRUG: Metformin and Lactic acidosis (4)
-----------------------------------------

Dear colleagues,

A brief answer: Though both the original manufacturer and later 
producers have tried to downplay the risk of lactic acidosis during 
treatment with metformin we should acknowledge that the risk - though 
rare - definitely exists and that there is epidemiological and 
historical proof that the relationship is a causative one. By 
historical proof I mean that the two predecessors of metformin - i.e. 
phenformin and buformin were linked to this particular adverse effect 
in a manner which left no room for doubt, and both were removed from 
the market for that and only that reason. There were up to 1991, the 
first edition of Colin Dollery's encyclopaedia "Therapeutic Drugs" 
more that ten scientific publications with a proven relationship, and 
a review over the years 1977-1982 mentioned 42 cases, of which 18 
(43%) were fatal. The predominant contraindication lying at the root 
of such accidents was mostly renal impairment, and not always severe. 

What the Dutch publication stresses and what I would like to 
emphasize again is that mild degrees of renal function impairment in 
the elderly can easily be overlooked because serum creatinine levels 
are within the "normal" range because the release of creatinine from 
muscle is much less than in younger people because muscle mass is so 
much smaller, and that accurately measuring renal clearance is 
difficult if there is no access to sophisticated laboratory 
facilities and measurements. And in addition all indirect estimates 
may be misleading. The risk is small but real, and the clinical 
diagnosis of lactic acidosis is difficult. The reality of life is 
that many people in developing countries will never reach the age of 
60, and in those who develop lactic acidosis death may be unavoidable 
once the diagnosis is made - often too late. 

So the main message remains: Be careful when prescribing metformin to elderly, frail and emaciated patients because occasionally the drug may be worse than the disease.

Regards,

Leo Offerhaus, 
the Netherlands
offerhausl@euronet.nl