title: Systematic review and meta-analysis of the efficacy and hypoglycemic safety of gliclazide versus other insulinotropic agents.
abstract: OBJECTIVE
  Sulfonylureas are well positioned in treating type 2 diabetes, after lifestyle modification and metformin. The sulfonylurea gliclazide was given preference over glibenclamide in older people with type 2 diabetes in the World Health Organization model list of essential medicines. Consequently, a systematic review and meta-analysis of randomized controlled trials of the efficacy and safety of gliclazide versus other oral insulinotropic agents (sulfonylureas, dipeptidyl peptidase-4 inhibitors, and glinides) was performed.
  
  
  METHODS
  Two reviewers searched MEDLINE for studies of ≥12 weeks duration in adults with type 2 diabetes. The key search word was "gliclazide", filtered with "randomized controlled trial", "human" and "19+ years". Differences were explored in mean change in glycated hemoglobin (HbA(1c)) from baseline (primary outcome) and risk of hypoglycemia (secondary outcome) between gliclazide and other oral insulinotropic agents; and other sulfonylureas.
  
  
  RESULTS
  Nine out of 181 references reported primary outcomes, of which 7 reported secondary outcomes. Gliclazide lowered HbA1c more than other oral insulinotropic agents, with a weighted mean difference of -0.11% (95%, CI -0.19 to -0.03%, P=0.008, I(2)=60%), though not more than other sulfonylureas (-0.12%; 95%, CI -0.25 to 0.01%, P=0.07, I(2)=77%). Risk of hypoglycemia with gliclazide was not different to other insulinotropic agents (RR 0.85; 95%, CI 0.66 to 1.09, P=0.20, I(2)=61%) but significantly lower than other sulfonylureas (RR 0.47; 95%, CI 0.27 to 0.79, P=0.004, I(2)=0%).
  
  
  CONCLUSIONS
  Compared with other oral insulinotropic agents, gliclazide significantly reduced HbA1c with no difference regarding hypoglycemia risk. Compared with other sulfonylureas, HbA1c reduction with gliclazide was not significantly different, but hypoglycemia risk was significantly lower.
authors.affiliation: Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: chansp@ummc.edu.my.
authors.forename: Siew Pheng
authors.initials: SP
authors.lastname: Chan
authors.affiliation: The Boden Institute, University of Sydney, Sydney, NSW, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Colagiuri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D005907:Gliclazide / Q000009:adverse effects / Q000627:therapeutic use*; D005905:Glyburide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000453:epidemiology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D005907:Gliclazide; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D013453:Sulfonylurea Compounds
keywords: Efficacy; Gliclazide; Hypoglycemia; Insulinotropic; Meta-analysis; Systematic review