Metformin--the gold standard in type 2 diabetes: what does the evidence tell us?

Metformin is a cornerstone of oral antidiabetic treatment. Recent joint American and European guidelines recommend instituting metformin therapy along with lifestyle modification at the time type 2 diabetes mellitus (T2DM) is diagnosed. Metformin acts to reduce hepatic gluconeogenesis and improve glucose uptake, and it may exert protective effects on pancreatic islet cells. Although metformin therapy produces substantial reductions in HbA1c, it does not produce body weight gain, is not associated with substantial risk for hypoglycaemia and has neutral to positive effects on lipids and blood pressure. The major adverse events associated with metformin are gastrointestinal. T2DM progresses even with initially effective monotherapy, and most patients will therefore receive combination therapy. When selecting agents to coadminister with metformin, a physician must consider efficacy in glycaemic control, safety, tolerability and any effects that may compromise overall efficacy (e.g. effects on body weight, lipids or blood pressure). In this regard, incretin-based therapies have characteristics that make them particularly suitable for add-on therapy with metformin.