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Hypoglycaemia when adding sulphonylurea to metformin: a systematic review and network meta‐analysis
Author(s) -
Andersen Stig Ejdrup,
Christensen Mikkel
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13059
Subject(s) - medicine , metformin , gliclazide , glimepiride , type 2 diabetes , randomized controlled trial , hypoglycemia , meta analysis , glibenclamide , relative risk , adverse effect , diabetes mellitus , glipizide , endocrinology , confidence interval , insulin
Aims The risk of hypoglycaemia may differ among sulphonylureas (SUs), but evidence from head‐to‐head comparisons is sparse. Performing a network meta‐analysis to use indirect evidence from randomized controlled trials (RCTs), we compared the relative risk of hypoglycaemia with newer generation SUs when added to metformin. Methods A systematic review identified RCTs lasting 12–52 weeks and evaluating SUs added to inadequate metformin monotherapy (≥1000 mg/day) in type 2 diabetes. Adding RCTs investigating the active comparators from the identified SU trials, we established a coherent network. Hypoglycaemia of any severity was the primary end point. Results Thirteen trials of SUs and 14 of oral non‐SU antihyperglycaemic agents (16 260 patients) were included. All reported hypoglycaemia only as adverse events. Producing comparable reductions in HbA 1C of −0.66 to −0.84% (−7 to −9 mmol/mol), the risk of hypoglycaemia was lowest with gliclazide compared to glipizide (OR 0.22, CrI: 0.05 to 0.96), glimepiride (OR 0.40, CrI: 0.13 to 1.27), and glibenclamide (OR 0.21, CrI: 0.03 to 1.48). A major limitation is varying definitions of hypoglycaemia across studies. Conclusions When added to metformin, gliclazide was associated with the lowest risk of hypoglycaemia between the newer generation SUs. Clinicians should consider the risk of hypoglycaemia agent‐specific when selecting an SU agent.