Mortality risk with sulphonylureas compared to metformin

Abstract

Current clinical guidelines in the USA and the UK recommend first-line glucose-lowering treatment with metformin monotherapy for glucose control in type 2 diabetes, where not contraindicated. Consequently, the proportion of people treated with sulphonylureas is decreasing. The purpose of this commentary is to discuss the risks and benefits associated with sulphonylurea monotherapy versus metformin monotherapy and the evidence that, in comparison with metformin, sulphonylureas cause increased harm to people with type 2 diabetes. Keywords: metformin, sulphonylureas, type 2 diabetes Date submitted 1 November 2013; date of first decision 2 January 2014; date of final acceptance 11 February 2014Current American Diabetes Association (ADA) and National Institute for Health and Care Excellence (NICE) guidelines in the UK recommend the use of metformin as first-line therapy for type 2 diabetes [1,2]. NICE suggests that a sulphonylurea should be considered as an option when the patient is not overweight, when metformin is contraindicated or not tolerated, or when a rapid response to therapy is required to combat hyperglycaemia symptoms [1]. However, the ADA makes no specific recommendation on the use of sulphonylureas to control type 2 diabetes, preferring to recommend the adoption of a more patient-centred approach based on financial cost, efficacy, potential side effects, patient preference and diabetes co-morbidities [1].In line with these clinical guidelines, the percentage of people with type 2 diabetes using sulphonylureas has decreased in both the UK and the USA. In the UK, the proportion of people with type 2 diabetes treated with sulphonylureas at any point in the natural history of their disease decreased from 45% in 1996 to 33% in 2005, and the number of people using metformin increased from 30% to 57% over the same period [3]. We have estimated that the proportion of people with type 2 diabetes in the UK using sulphonylurea monotherapy first-line was 5% in 2012 (see Figure 1, unpublished data). Between 2000 and 2010, the number of people using sulphonylurea monotherapy second-line following failure with metformin monotherapy decreased from 12% in 2000 to 7% in 2010 [4]. In the USA, the percentage of patients initially treated with sulphonylureas decreased from 26% in 2006 to 18% in 2008, whereas the proportion of patients starting therapy with metformin increased from 51% to 65% [5]. However, metformin has only been licensed by the US FDA since 1995 [6]. A decrease in the prescribing of sulphonylureas and an increase in the prescribing of metformin have also been observed in Germany, Italy and Japan [7][8][9][10].Since the publication of the results from the University Group Diabetes Programme (UGDP) in 1969, there has been controversy surrounding the use of sulphonylureas to lower blood glucose in people with type 2 diabetes. In this large, multicentre, placebo-controlled trial, patients were randomized to placebo plus diet, fixed-dose tolbutamide (a first-generation sulphonylurea), fixed-dose insulin or a va...

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Clinical Update: Cardiovascular Disease in Diabetes Mellitus

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