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The history of the biguanide metformin is interesting. Although first synthesised over ninety years ago and known to have glucose lowering properties, its potential as a therapeutic agent in the treatment of diabetes was either ignored or forgotten about until the 1970s. It has now become perhaps the most widely prescribed oral anti-diabetic drug worldwide. It is easy to appreciate the reasons for its popularity. It is relatively cheap and has a proven effectiveness in improving glycaemic control in patients with type 2 diabetes (T2DM). It has, in addition, desirable cardiovascular protective properties and can enable prevention of weight gain. The drug has a reasonable safety profile as it has a low risk of causing significant hypoglycaemia; the more commonly described adverse effects are gastro-intestinal (described as being mild and short lived although many patients would dispute this) and a tendency to cause lactic acidosis in well described circumstances which admittedly are rare and preventable. In many respects therefore, metformin …

Which oral agent to use when metformin is no longer effective?