Metformin: actions and indications for use in non-insulin-dependent diabetes mellitus

Metformin (N,N-dimethylbiguanide) is about to be introduced into the United States. The drug, a potent blood glucose-lowering agent, is rapidly absorbed through the small intestine, has a circulating t 1/2 in plasma of 1.7 to 2.5 hours, and is 90% cleared through the kidneys in 12 hours. The drug does not cause hypoglycemia in nondiabetic patients and is effective in both obese and nonobese patients with non-insulin-dependent diabetes mellitus (NIDDM). The drug does not act through stimulation of endogenous insulin secretion. It seems to act at multiple sites, with a small effect on the inhibition of intestinal glucose transport, a moderate effect on inhibition of hepatic glucose output, and a major effect on enhancement of peripheral glucose uptake by muscle and adipose tissues. In addition to its glucose-lowering potency, metformin causes weight loss in obese patients with NIDDM and lowers total cholesterol, very-low-density lipoprotein cholesterol, total triglycerides, and very-low-density lipoprotein triglyceride levels as well as causing an increase in high-density lipoprotein cholesterol level. The drug is ideally suited for obese patients with NIDDM who are unresponsive to diet alone, and it is effective in combination with sulfonylureas. The major risk associated with use of metformin is the development of lactic acidosis. Patients predisposed toward the development of lactic acidosis are those with hepatic or renal disease or with tissue ischemia, in whom the drug should not be prescribed.