Metformin: mechanisms of antihyperglycemic action, other pharmacodynamic properties, and safety perspectives

Abstract

Objective: To characterize the mechanisms of action of metformin and describe its effects and safety profile.

Methods: Results of more than 30 years of clinical use in countries other than the United States are summarized. In addition, the pharmacologic properties of metformin are compared with those of other antihyperglycemic agents.

Results: Approximately 90% of all cases of diabetes are non-insulin-dependent diabetes mellitus (NIDDM)--a heterogeneous disease that involves several pathogenic factors and is associated with other coexisting conditions, such as cardiovascular disease, hypertension, and obesity. Thus, an agent that controls blood glucose levels and has favorable effects on the concomitant conditions should be considered when pharmacologic intervention is needed for the treatment of NIDDM. Metformin possesses the pharmacodynamic properties to do both. Its mechanisms of action include the reduction of hepatic glucose production and enhancement of peripheral glucose disposal, making metformin an effective antihyperglycemic agent. It also has other pharmacologic properties, independent of its glycemic effects, that offer additional clinical benefits in comparison with other pharmacologic NIDDM treatments. These benefits include stabilization or even loss of weight in patients for whom weight gain is a concern and reduction of plasma lipid levels in patients with hyperlipidemia.

Conclusion: On the basis of 3 decades of clinical experience, metformin has been shown to be not only a well tolerated but also a highly effective antihyperglycemic agent.