Metformin is the First Medication To Use for Type 2 Diabetes   (June 5, 2011)

A recent report again reaffirms that metformin is the first medication to use when a patient with type 2 diabetes (T2D) needs help with lowering blood glucose levels. The 200+ page report, Oral Diabetes Medications for Adults With Type 2 Diabetes: An Update, was prepared for the Agency for Healthcare Research and Quality by the Johns Hopkins University Evidence-based Practice Center. It is loaded with tables and discussions, but the conclusion is strikingly brief: "Although the long-term benefits and harms of diabetes medications remain unclear, the evidence supports use of metformin as a firstline agent. Comparisons of two-drug combinations showed little to no difference in HbA1c reduction, but some combinations increased risk for hypoglycemia and other adverse events."

To summarize the findings from the report: An older diabetes drug, metformin, works better, and has fewer side effects than newer drugs for T2D. It's also cheaper, as it's been available as a generic for years (in fact, it's so cheap that some supermarkets give it away). Metformin rarely causes hypoglycemia, isn't associated with weight gain as some other diabetes drugs are. Reasons to avoid metformin are relatively rare, primarily avoidance of its use in patients with renal disease, to avoid the rare and potentially fatal side effect of lactic acidosis. It can cause gastrointestinal distress, and doses should be raised slowly to help protect from gut side effects. And if a second diabetes drug is needed to control blood sugar levels, the second drug should be added to metformin. 

This is essentially the same conclusion as had been reached in a consensus statement published in 2006 and updated in 2008 by the American Diabetes Association and the European Association for the Study of Diabetes, Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy. Those authors suggested that the first step in the management of T2DM should be lifestyle intervention plus metformin, and the second should be addition of a second medication.

Is there any reason for physicians to start with alternate diabetes drugs rather than metformin? In my opinion, only if the patient has impaired kidney function, or can't tolerate metformin because of overwhelming gastrointestinal symptoms (which may include diarrhea, gas, indigestion/stomach upset, and nausea and vomiting). 

There are eleven classes of diabetes drugs. The first-choice drug for most patients with T2D is clearly metformin; all of the other 10 classes of diabetes drugs can be considered as second-line drugs.