Treatment of non-insulin-dependent diabetes mellitus with metformin.

BACKGROUND Metformin alleviates hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM) by inhibiting hepatic glucose production and improving peripheral insulin sensitivity. In contrast to sulfonylureas, metformin does not stimulate insulin-secretion, promote weight gain, exacerbate hyperinsulinemia, or cause hypoglycemia. It also favorably affects serum lipids. METHODS A comprehensive review of the medical literature from 1968 to the present was conducted using the key words "metformin" and "non-insulin-dependent diabetes mellitus." RESULTS Metformin monotherapy was superior to placebo and comparable to sulfonylureas in reducing fasting plasma glucose and glycosylated hemoglobin levels in patients with NIDDM uncontrolled by diet. Metformin and sulfonylureas, however, had diverse effects on body weight and fasting plasma insulin levels; both weight and insulin levels remained unchanged or decreased with metformin and increased with sulfonylureas. In patients with secondary sulfonylurea failure, the combination of metformin and a sulfonylurea synergistically improved glycemic control better than either drug alone and was comparable to insulin plus sulfonylurea. When hyperglycemia is uncontrolled by insulin after secondary sulfonylurea failure, limited data suggest the efficacy of metformin plus insulin. The mild, transient, self-limited gastrointestinal side effects that sometimes occur can be minimized by gradually increasing the doses and by taking metformin with food. Risk of metformin-associated lactic acidosis is low if prescribing guidelines are adhered to. Potential adverse drug interactions include hypoglycemia during concurrent sulfonylurea therapy and elevated metformin plasma concentrations when metformin is taken concomitantly with cimetidine. CONCLUSIONS Metformin can be used safely and effectively as first-line monotherapy in NIDDM or in combination with a sulfonylurea when monotherapy with either agent fails. It can be particularly suitable when weight gain, hyperlipidemia, and hypoglycemia are clinically important issues.