Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study

Abstract

Both sulphonylureas (SU) and metformin (MET) reduce hyperglycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus, but they do so by entirely different mechanisms. Therefore, SU and MET can be combined, and a few controlled studies have shown pronounced reductions in hyperglycaemia following treatment with this combination [1±3]. As SU and MET also have beneficial long-term effects on diabetic microvascular disease [4,5] and MET even on macrovascular disease [5], it would seem logical to presume that the combination of SU and MET would be highly beneficial for ischaemic heart disease (IHD) and stroke in patients with Type II diabetes. A UKPDS substudy instead reported a higher risk of diabetes-related death with this type of combination therapy compared with SU therapy alone [5]. Therefore, we decided to analyse cause- Diabetologia (2000) 43: 558±560 Articles Short communicationIncreased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study

Comment on: Evans JMM, Ogston SA, Emslie-Smith A, Morris AD (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

“…The same group of investigators demonstrated in another two studies [5,6] using the same database that, compared with sulfonylurea monotherapy, the combination of sulfonylurea and metformin is associated with a reduced risk of mortality. These findings are in contrast to those reported by Olsson and co-workers [7], also referred to by Tayek in his letter [1]. Although Olsson and colleagues reported that mortality was increased in diabetic patients given a combination of sulfonylurea and metformin compared with those patients given sulfonylurea alone, this study involved far fewer patients than the study by Johnson et al [6].…”

“…Although Olsson and colleagues reported that mortality was increased in diabetic patients given a combination of sulfonylurea and metformin compared with those patients given sulfonylurea alone, this study involved far fewer patients than the study by Johnson et al [6]. Moreover, Olsson et al [7] state that the observed increased mortality in the combination group may be secondary to a more aggressive type of diabetes. This again highlights the difficulty involved in interpreting observational studies lacking corresponding control groups.…”

Comment on: Evans JMM, Ogston SA, Emslie-Smith A, Morris AD (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

“…In 1998, a UK prospective diabetes study demonstrated that the addition of a sulfonylurea (glibenclamide or chlorpropamide) to metformin therapy increased mortality by 60% (3.0 vs 1.9 per 100 patient-years; p< 0.05) [5]. A similar 1.63-fold increase in mortality was seen in diabetic patients given combination therapy with a sulfonylurea plus metformin compared with sulfonylurea alone [6]. Of interest was the fact that aggressive therapy with metformin alone reduced mortality compared with aggressive therapy with conventional medications (1.3 vs 2.1% per 100 patient-years) [5].…”

Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

“…Another worrying result was a 96% increase in diabetes-related deaths in sulfonylureatreated patients with addition of metformin [6]. Observational studies have shown increased risks associated with a combination of metformin and sulfonylureas, but have been unable to account fully for underlying differences between patients in different therapy groups [7,8]. In contrast, a more recent study found no increased risk of mortality among patients who were prescribed sulfonylureas and metformin in combination, compared with those prescribed either drug as monotherapy [9].…”