title: Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X).
abstract: OBJECTIVE
  To compare efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled with metformin.
  
  
  METHODS
  Adults with diabetes inadequately controlled (HbA1c 7-10%) with metformin were randomized to lixisenatide 20 μg once daily (n=318) or exenatide 10 μg twice daily (n=316) in a 24-week (main period), open-label, parallel-group, multicenter study. The primary objective was a noninferiority assessment of lixisenatide versus exenatide in HbA1c change from baseline to week 24.
  
  
  RESULTS
  Lixisenatide once daily demonstrated noninferiority in HbA1c reduction versus exenatide twice daily. The least squares mean change was -0.79% (mean decrease 7.97 to 7.17%) for lixisenatide versus -0.96% (mean decrease 7.96 to 7.01%) for exenatide, and treatment difference was 0.17% (95% CI, 0.033-0.297), meeting a predefined noninferiority upper CI margin of 0.4%. Responder rate (HbA1c<7.0%) and improvements in fasting plasma glucose were comparable. Both agents induced weight loss (from 94.5 to 91.7 kg and from 96.7 to 92.9 kg with lixisenatide and exenatide, respectively). Incidence of adverse events (AEs) was similar for lixisenatide and exenatide, as was incidence of serious AEs (2.8 and 2.2%, respectively). Discontinuations attributable to AEs occurred in 33 lixisenatide (10.4%) and 41 exenatide (13.0%) patients. In the lixisenatide group, fewer participants experienced symptomatic hypoglycemia (2.5 vs. 7.9%; P<0.05), with fewer gastrointestinal events (especially nausea; 24.5 vs. 35.1%; P<0.05).
  
  
  CONCLUSIONS
  Add-on lixisenatide once daily in type 2 diabetes inadequately controlled with metformin demonstrated noninferior improvements in HbA1c, with slightly lower mean weight loss, lower incidence of hypoglycemia, and better gastrointestinal tolerability compared with exenatide twice daily.
authors.affiliation: Corresponding author: Julio Rosenstock, juliorosenstock@dallasdiabetes.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.forename: Denis
authors.initials: D
authors.lastname: Raccah
authors.forename: László
authors.initials: L
authors.lastname: Korányi
authors.forename: Laura
authors.initials: L
authors.lastname: Maffei
authors.forename: Gabor
authors.initials: G
authors.lastname: Boka
authors.forename: Patrick
authors.initials: P
authors.lastname: Miossec
authors.forename: John E
authors.initials: JE
authors.lastname: Gerich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D010455:Peptides; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor