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Uses of Metformin May Extend Beyond Patients with Type 2 Diabetes

The insulin-sensitising drug metformin is useful in a variety of insulin-resistant and prediabetic conditions, including impaired glucose tolerance, obesity, polycystic ovary syndrome and metabolic abnormalities associated with HIV disease.

Ripudaman S. Hundal, MD, with the Diabetes & Metabolic Disease Center, Christiana Care, Wilmington, Delaware, and Silvio E. Inzucchi with Yale University, New Haven, Connecticut, United States, reviewed the role and benefits of metformin use in various settings.

According to the authors, the benefits and safety record of metformin, have led investigators to consider the use of metformin in insulin-resistant states even before the development of frank hyperglycaemia.

Unlike sulfonylureas, metformin does not stimulate insulin secretion. The primary mechanism through which metformin exerts an antihyperglycaemic effect is thought to be through decreased hepatic glucose production. It may also improve peripheral insulin sensitivity and decrease intestinal glucose absorption.

About half of patients taking metformin experience temporary gastrointestinal effects. However, a long-acting preparation may reduce this incidence. The adverse effect of greatest concern is lactic acidosis, which occurs in 1 per 30,000 patient-years of use.

In type 2 diabetics, metformin appears to decrease plasma fasting glucose and HbA1c levels without causing weight gain. Metformin may also have a positive influence on a variety of cardiovascular risk factors and may be useful in preventing diabetes in overweight individuals with mild hyperglycaemia.

Metformin is being investigated for use in women with polycystic ovary syndrome (PCOS) to stimulate ovarian function, HIV-associated metabolic abnormalities associated with treatment, and non-alcoholic steatohepatitis.

"Metformin is a popular, generally well-tolerated, effective antihyperglycaemic agent with demonstrated benefit on vascular risk and outcomes in patients with diabetes," the authors conclude. "As a result, many consider it the optimal treatment of choice in a patient with type 2 diabetes which remains suboptimally controlled despite diet and exercise," they add.

They suggest that while further study is necessary before more widespread use is encouraged, the role of metformin may be expanded for glucose control in children and teenagers with type 2 diabetes, in non-diabetic women with PCOS, and to prevent progression to diabetes.

Both authors have received financial support from Bristol-Myers Squibb Company and other commercial sources.
Drugs 2003;63:18:1879-1894. "Metformin: new understandings, new uses"

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