title: Efficacy and Acceptability of Glycemic Control of Glucagon-Like Peptide-1 Receptor Agonists among Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.
abstract: To synthesize current evidence of the impact of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on hypoglycemia, treatment discontinuation and glycemic level in patients with type 2 diabetes.
  
  
  
  Systematic review and network meta-analysis.
  
  
  
  Literature search (Medline, Embase, the Cochrane library), website of clinical trial, bibliographies of published systematic reviews.
  
  
  
  Randomized controlled trials with available data comparing GLP-1 RAs with placebo or traditional anti-diabetic drugs in patients with type 2 diabetes.
  
  
  
  Traditional pairwise meta-analyses within DerSimonian-Laird random effects model and network meta-analysis within a Bayesian framework were performed to calculate odds ratios for the incidence of hypoglycemia, treatment discontinuation, HbA1c<7.0% and HbA1c<6.5%. Ranking probabilities for all treatments were estimated to obtain a treatment hierarchy using the surface under the cumulative ranking curve (SUCRA) and mean ranks.
  
  
  
  78 trials with 13 treatments were included. Overall, all GLP-1 RAs except for albiglutide increased the risk of hypoglycemia when compared to placebo. Reduction in the incidence of hypoglycemia was found for all GLP-1 RAs versus insulin (except for dulaglutide) and sulphonylureas. For the incidence of treatment discontinuation, increase was found for exenatide, liraglutide, lixisenatide and taspoglutide versus placebo, insulin and sitagliptin. For glycemic level, decrease was found for all GLP-1 RAs versus placebo. Dulaglutide, exenatide long-acting release (exe_lar), liraglutide and taspoglutide had significant lowering effect when compared with sitagliptin (HbA1c<7.0%) and insulin (HbA1c<6.5%). Finally, according to SUCRAs, placebo, thiazolidinediones and albiglutide had the best decrease effect on hypoglycemia; sulphanylureas, sitagliptin and insulin decrease the incidence of treatment discontinuation most; exe_lar and dulaglutide had the highest impact on glycemic level among 13 treatments.
  
  
  
  Among 13 treatments, GLP-1 RAs had a significant reduction with glycemic level but a slight increase effect on hypoglycemia and treatment discontinuation. While albiglutide had the best decrease effect on hypoglycemia and treatment discontinuation among all GLP-1 RAs. However, further evidence is necessary for more conclusive inferences on mechanisms underlying the rise in hypoglycemia.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, ON, Canada.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Quan
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Center for Evidence-based and Translational Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Xiantao
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Endocrinology and Metabolism, People's Hospital, Peking University, Beijing, China.
authors.forename: Linong
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
authors.forename: Siyan
authors.initials: S
authors.lastname: Zhan
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D001786:Blood Glucose; D000097789:Glucagon-Like Peptide-1 Receptor Agonists