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

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. 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 A₁C (HbA₁C), 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. Six studies including 1364 patients were identified. Based on random effects meta-analysis, the pooled estimate of change in HbA₁C 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. This analysis has demonstrated that, in patients with type 2 diabetes whose control is inadequate on metformin monotherapy, the magnitude of incremental HbA₁C 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.