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BACKGROUND: The usefulness of metformin as an oral antidiabetic agent is widely accepted. However, several other classes of oral antidiabetic agents have been recently introduced, raising the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs for treatment of type 2 diabetes mellitus (DM). METHODS: Synthesis of information was preceded by a comprehensive review of the English language literature using Medline. We also reviewed bibliographies of relevant articles. The studies most pertinent to the mechanism of action, efficacy, toxicity and administration of metformin were selected for citation in this review. RESULTS: Metformin acts by increasing tissue sensitivity to insulin, principally in the liver. Beneficial properties of metformin include weight reduction, favourable effects on the lipid profile and the fibrinolytic pathway, and improvement of ovarian function in some insulin-resistant women. It does not cause hyperinsulinaemia or hypoglycaemia. Metformin is effective as monotherapy and, in combination with both insulin secretagogues and thiazolidinediones (TZDs), may obviate the need for insulin treatment. Several fixed-dose combination pills containing metformin and other agents are available. A protocol for the initiation of therapy with contemporary oral agents for type 2 DM is presented, with emphasis on the continuing central role of metformin. CONCLUSIONS: Metformin remains a safe and effective agent for the therapy of patients with type 2 DM. It is useful as monotherapy or in combination regimens with the newer insulin secretagogues, TZDs or insulin. It is still in most circumstances the agent of choice for initial therapy of the typical obese patient with type 2 DM and mild to moderate hyperglycaemia.
Goodarzi et al. (Mon,) studied this question.