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Michael Bannon, Which oral agent to use when metformin is no longer effective?, QJM: An International Journal of Medicine, Volume 104, Issue 3, March 2011, Pages 183–184, https://doi.org/10.1093/qjmed/hcr015
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Extract
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 is almost an ideal therapeutic agent. Sadly, the experience of both patients and clinicians is that following an initial period of improved glycaemic control, it slowly fails to be effective when used on its own. The next step for many T2DM patients is to combine the use of metformin with insulin or another oral anti-diabetic agent. The review by Vella et al., considers the additional and alternative oral anti-diabetic therapeutic options that are currently available. Several families of anti-diabetic drugs are appraised in terms of known mode of action, effectiveness and safety. The sulphonylureas have the advantage of familiarity and low cost but are associated with hypoglycaemia and weight gain. The so-called gliptins represent a newer class of oral hypoglycaemic agent which appear to have a neutral effect on weight and an acceptable safety profile; however their cardiovascular effects are as yet uncertain. The glitazones have been shown to effectively reduce insulin resistance but some drugs in this category have been withdrawn because of an apparent increased risk of adverse cardiovascular events. Glucagon-like peptide (GLP-1) agonists represent a newer class of anti-diabetic agent that increases insulin secretion in response to food and which have a low risk for weight gain and hypoglycaemia. The authors conclude that at present metformin represents the best available drug for first line treatment of T2DM but none of the other available agents can be considered as a preferred option for second line “add-in” treatment.
