Type 2 diabetes mellitus results from impaired insulin secretion and reduced peripheral insulin sensitivity. Treatment options include diet, oral antihyperglycemic agents, and insulin. Metformin, an oral biguanide, ameliorates hyperglycemia by improving peripheral sensitivity to insulin, and reducing gastrointestinal glucose absorption and hepatic glucose production. Unlike sulfonylureas, it does not stimulate insulin secretion, aggravate hyperinsulinemia, or cause hypoglycemia or weight gain (weight stabilizes or decreases). It also has beneficial effects on serum lipid profiles. In lean or overweight type 2 diabetic patients uncontrolled by diet, metformin monotherapy significantly improves glycemic control, compared with placebo, and to similar extents as sulfonylurea monotherapy. In secondary sulfonylurea failure, combination metformin-sulfonylurea treatment significantly improves glycemic control beyond that achieved with either agent alone. Metformin-sulfonylurea also appears to be as effective as insulin or insulin plus sulfonylurea, suggesting that such combination therapy may obviate or substantially delay insulin therapy. Limited data suggest that metformin-insulin therapy may improve glycemic control, possibly reducing insulin requirements, in type 2 diabetic patients uncontrolled by insulin alone following secondary sulfonylurea failure. Gastrointestinal side effects are common, but usually tolerated. Lactic acidosis risk is minimal, provided that contraindications, particularly renal impairment, and prescribing guidelines are respected. Aside from elevated plasma metformin levels with cimetidine and synergistic hypoglycemia with sulfonylureas, few interactions occur. Thus, metformin is safe and effective both as monotherapy or in combination with other antihyperglycemic agents in type 2 diabetic patients requiring additional glycemic control, and may be advantageous when weight control is desirable and/or hyperlipidemia exists. (C) 1997 by Excerpta Medica, Inc.
