Estimating the effect of sulfonylurea on HbA^sub 1c^ in diabetes: a systematic review and meta-analysis

• Published in: Diabetologia Vol. 56; no. 5; p. 973
• Main Authors: Hirst, J A, Farmer, A J, Dyar, A, Lung, T W; C, Stevens, R J
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.05.2013
• Subjects: Clinical trials; Diabetes; Glucose; Insulin; Meta-analysis; Primary care; Systematic review; United Kingdom > UK
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-013-2856-6

Sulfonylureas are widely prescribed glucose-lowering medications for diabetes, but the extent to which they improve glycaemia is poorly documented. This systematic review evaluates how sulfonylurea treatment affects glycaemic control. Medline, EMBASE, the Cochrane Library and clinical trials registries were searched to identify double-blinded randomised controlled trials of fixed-dose sulfonylurea monotherapy or sulfonylurea added on to other glucose-lowering treatments. The primary outcome assessed was change in HbA^sub 1c^, and secondary outcomes were adverse events, insulin dose and change in body weight. Thirty-one trials with a median duration of 16Â weeks were included in the meta-analysis. Sulfonylurea monotherapy (nine trials) lowered HbA^sub 1c^ by 1.51% (17Â mmol/mol) more than placebo (95% CI, 1.25, 1.78). Sulfonylureas added to oral diabetes treatment (four trials) lowered HbA^sub 1c^ by 1.62% (18Â mmol/mol; 95% CI 1.0, 2.24) compared with the other treatment, and sulfonylurea added to insulin (17 trials) lowered HbA^sub 1c^ by 0.46% (6Â mmol/mol; 95% CI 0.24, 0.69) and lowered insulin dose. Higher sulfonylurea doses did not reduce HbA^sub 1c^ more than lower doses. Sulfonylurea treatment resulted in more hypoglycaemic events (RR 2.41, 95% CI 1.41, 4.10) but did not significantly affect the number of other adverse events. Trial length, sulfonylurea type and duration of diabetes contributed to heterogeneity. Sulfonylurea monotherapy lowered HbA^sub 1c^ level more than previously reported, and we found no evidence that increasing sulfonylurea doses resulted in lower HbA^sub 1c^. HbA^sub 1c^ is a surrogate endpoint, and we were unable to examine long-term endpoints in these predominately short-term trials, but sulfonylureas appear to be associated with an increased risk of hypoglycaemic events.[PUBLICATION ABSTRACT]