title: Safety and efficacy of gliclazide as treatment for type 2 diabetes: a systematic review and meta-analysis of randomized trials.
abstract: OBJECTIVE
  Gliclazide has been associated with a low risk of hypoglycemic episodes and beneficial long-term cardiovascular safety in observational cohorts. The aim of this study was to assess in a systematic review and meta-analysis of randomized controlled trials the safety and efficacy of gliclazide compared to other oral glucose-lowering agents (PROSPERO2013:CRD42013004156).
  
  
  METHODS
  Medline, EMBASE, Clinicaltrials.gov, Trialregister.nl, Clinicaltrialsregister.eu and the Cochrane database.
  
  
  METHODS
  Included were randomized studies of at least 12 weeks duration with the following outcomes: HbA1c change, incidence of severe hypoglycemia, weight change, cardiovascular events and/or mortality when comparing gliclazide with other oral blood glucose lowering drugs. Bias was assessed with the Cochrane risk of bias tool. The inverse variance random effects model was used.
  
  
  RESULTS
  Nineteen trials were included; 3,083 patients treated with gliclazide and 3,155 patients treated with other oral blood glucose lowering drugs. There was a considerable amount of heterogeneity between and bias in studies. Compared to other glucose lowering agents except metformin, gliclazide was slightly more effective (-0.13% (95%CI: -0.25, -0.02, I(2) 55%)). One out of 2,387 gliclazide users experienced a severe hypoglycemic event, whilst also using insulin. There were 25 confirmed non-severe hypoglycemic events (2.2%) in 1,152 gliclazide users and 22 events (1.8%) in 1,163 patients in the comparator group (risk ratio 1.09 (95% CI: 0.20, 5.78, I² 77%)). Few studies reported differences in weight and none were designed to evaluate cardiovascular outcomes.
  
  
  CONCLUSIONS
  The methodological quality of randomized trials comparing gliclazide to other oral glucose lowering agents was poor and effect estimates on weight were limited by publication bias. The number of severe hypoglycemic episodes was extremely low, and gliclazide appears at least equally effective compared to other glucose lowering agents. None of the trials were designed for evaluating cardiovascular outcomes, which warrants attention in future randomized trials.
authors.affiliation: Diabetes Centre Zwolle, Zwolle, The Netherlands.
authors.forename: Gijs W D
authors.initials: GW
authors.lastname: Landman
authors.affiliation: Department of Epidemiology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Geertruide H
authors.initials: GH
authors.lastname: de Bock
authors.affiliation: Diabetes Centre Zwolle, Zwolle, The Netherlands.
authors.forename: Kornelis J J
authors.initials: KJ
authors.lastname: van Hateren
authors.affiliation: Diabetes Centre Zwolle, Zwolle, The Netherlands.
authors.forename: Peter R
authors.initials: PR
authors.lastname: van Dijk
authors.affiliation: Department of General Practice, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Klaas H
authors.initials: KH
authors.lastname: Groenier
authors.affiliation: Department Internal Medicine, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Rijk O B
authors.initials: RO
authors.lastname: Gans
authors.affiliation: Diabetes Centre Zwolle, Zwolle, The Netherlands.
authors.forename: Sebastiaan T
authors.initials: ST
authors.lastname: Houweling
authors.affiliation: Diabetes Centre Zwolle, Zwolle, The Netherlands ; Department Internal Medicine, University Medical Centre Groningen, Groningen, The Netherlands ; Department of Internal Medicine, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Henk J G
authors.initials: HJ
authors.lastname: Bilo
authors.affiliation: Diabetes Centre Zwolle, Zwolle, The Netherlands.
authors.forename: Nanne
authors.initials: N
authors.lastname: Kleefstra
mesh_terms: D000284:Administration, Oral; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005907:Gliclazide / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D005907:Gliclazide