title: Hypoglycaemia when adding sulphonylurea to metformin: a systematic review and network meta-analysis.
abstract: 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.
  
  
  
  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.
  
  
  
  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 HbA1Cof -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.
  
  
  
  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.
authors.affiliation: Clinical Pharamcology Unit, Zealand University Hospital, DK-4000, Roskilde, Denmark. seja@regionsjaelland.dk.
authors.forename: Stig Ejdrup
authors.initials: SE
authors.lastname: Andersen
authors.affiliation: Department of Clinical Pharmacology, Bispebjerg University Hospital, DK-2400, Copenhagen NV, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Christensen
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004359:Drug Therapy, Combination / Q000009:adverse effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000009:adverse effects; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D013453:Sulfonylurea Compounds / Q000009:adverse effects*
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: hypoglycaemia; network meta-analysis; oral antiglycaemic agents; relative safety; sulphonylurea; type 2 diabetes