Metformin is unanimously considered a first-line
glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with
type 2 diabetes because of numerous
contraindications that could lead to an increased risk of
lactic acidosis. Various observational data from real-life have shown that many diabetic patients considered to be at risk still receive
metformin and often without appropriate dose adjustment, yet apparently with no harm done and particularly no increased risk of
lactic acidosis. More interestingly, recent data have suggested that
type 2 diabetes patients considered at risk because of the presence of traditional
contraindications may still derive benefit from
metformin therapy with reductions in morbidity and mortality compared with other
glucose-lowering agents, especially sulphonylureas. The present review analyzes the benefit-risk balance of
metformin therapy in special populations, namely, patients with stable
coronary artery disease,
acute coronary syndrome or
myocardial infarction,
congestive heart failure, renal impairment or
chronic kidney disease, hepatic dysfunction and chronic
respiratory insufficiency, all conditions that could in theory increase the risk of
lactic acidosis. Special attention is also paid to elderly patients with
type 2 diabetes, a population that is growing rapidly, as older patients can accumulate several comorbidities classically considered
contraindications to the use of
metformin. A review of the recent scientific literature suggests that reassessment of the
contraindications of
metformin is now urgently needed to prevent physicians from prescribing the most popular
glucose-lowering
therapy in everyday clinical practice outside of the official recommendations.