Metformin has been used for over 40 years as an effective
glucose-lowering agent in type
2 (noninsulin-dependent) diabetes mellitus. Typically it reduces basal and postprandial hyperglycaemia by about 25% in more than 90% of patients when either given alone or coadministered with other
therapies including
insulin during a programme of managed care.
Metformin counters
insulin resistance and offers benefits against many features of the
insulin resistance syndrome (Syndrome X) by preventing bodyweight gain, reducing hyperinsulinaemia and improving the
lipid profile. In contrast to sulphonylureas,
metformin does not increase insulin secretion or cause serious hypoglycaemia. Treatment of
type 2 diabetes mellitus with
metformin from diagnosis also offers greater protection against the chronic vascular complications of
type 2 diabetes mellitus. The most serious complication associated with
metformin is
lactic acidosis which has an incidence of about 0.03 cases per 1000 patients years of treatment and a mortality risk of about 0.015 per 1000 patient-years. Most cases occur in patients who are wrongly prescribed the
drug, particularly patients with impaired renal function (e.g. serum
creatinine level > 130 micromol/L or > 1.5 g/L). Other major
contraindications include
congestive heart failure, hypoxic states and advanced
liver disease. Serious adverse events with
metformin are predictable rather than spontaneous and are potentially preventable if the prescribing guidelines are respected. Gastrointestinal adverse effects, notably diarrhoea, occur in less than 20% of patients and remit when the dosage is reduced. The life-threatening risks associated with
metformin are rare and could mostly be avoided by strict adherence to the prescribing guidelines. Given the 4 decades of clinical experience with
metformin, its antihyperglycaemic efficacy and benefits against Syndrome X,
metformin offers a very favourable risk-benefit assessment when compared with the chronic morbidity and premature mortality among patients with
type 2 diabetes mellitus.