The aims of this review are to precise the pathophysiological mechanisms leading to
biguanide-associated
lactic acidosis, to give elements of diagnosis, and to underline the precautionary conditions for prescribing these drugs by an improvement in physicians and patient's education.
DATA SOURCES: Data in selected articles were reviewed, clinical and basic science research relevant informations were extracted.
DATA SYNTHESIS:
Metformin, which is an oral
antidiabetic agent, is the only one
biguanide available in France. It acts by enhancing the sensitivity to
insulin by a decrease in the hepatic
glucose production and an increase in its peripheral use. In term of
glycemic control, it has the same efficiency than the other
hypoglycemic agents. It represents the treatment of choice for
overweight type 2 diabetic patients because of its beneficial effects on the
weight loss and on the cardiovascular complications. The incidence of
metformin-associated
lactic acidosis is very low when contra-indications and appropriate rules for prescribing this
drug are respected. The relationship between
metformin and
lactic acidosis remains largely controversial. In practical, we can distinguish three situations which have different prognosis. In the first case,
metformin seems to be responsible for
lactic acidosis because of self-
poisoning or accidental overdose, and prognosis is good. In the second case, the association between
metformin and
lactic acidosis is coincidental rather than causal, and may be induced by an underlying organ failure. In the last case there is a cause of
lactic acidosis which is worsened by a precipitating factor leading to
metformin accumulation. The 2 latter situations are very severe as mortality rate is about 50%. Symptomatic treatments and
renal replacement therapy which allows
metformin removal are the curative treatment. Prevention is essential. It requires the respect of
metformin contraindications and a better education of physicians and patients for a safe prescription.
CONCLUSION: Due to its beneficial effects,
metformin is the gold standard treatment for
overweight type 2 diabetic patients. The essential precautionary conditions for prescribing
metformin as well as the respect of its contra-indications permit largely to prevent
lactic acidosis. This complication is serious when it is associated with intercurrent illnesses and
metformin accumulation. The curative treatment is based on
renal replacement therapy. Prevention only rests on the respect of the contra-indications. Education of physicians and patients concerning the rules of prescription remains essential.