Glycaemic control and adverse events in patients with type 2 diabetes treated with metformin plus sulphonylurea: a meta-analysis

Aim: The aim of this study was to quantify the effect of a sulphonylurea on glycaemic control and the risk adverse events when incorporated into the treatment regimen of patients with type 2 diabetes inadequately controlled on metformin. Methods: A systematic review was carried out to identify randomized controlled trials of sulphonylurea therapy in patients with type 2 diabetes whose glycaemic control was inadequate after maximal treatment with metformin. Data on reductions in haemoglobin A(1C) (HbA(1C)), fasting plasma glucose (FPG) and risk of hypoglycaemic events were extracted from each study and pooled in meta-analyses. Data on weight change were also extracted and tabulated. Results: Six studies including 1364 patients were identified. Based on random effects meta-analysis, the pooled estimate of change in HbA(1C) from baseline was 0.9% (95% CI 0.7-1.1, p = 0.00011 vs. baseline) and for change in FPG from baseline was 1.8 mmol/l (95% CI 1.1-2.5, p = 0.0026 vs. baseline). The odds of experiencing a hypoglycaemic event was significantly higher in sulphonylurea-treated patients than in those on comparator treatments (OR = 5.3, 95% CI 1.7-16.3, p = 0.03). Mean weight change ranged from +2.5 to -0.1 kg, depending on the comparator treatment. Conclusions: This analysis has demonstrated that, in patients with type 2 diabetes whose control is inadequate on metformin monotherapy, the magnitude of incremental HbA(1C) reduction achieved by the addition of a sulphonylurea is unlikely to exceed 1%, even after titration to maximum tolerated doses. Additionally, clinically relevant side-effects such as symptomatic hypoglycaemia and weight gain may be experienced.