title: Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1).
abstract: OBJECTIVE
  To assess the efficacy and safety of one- and two-step dose-increase regimens of lixisenatide once daily in participants with Type 2 diabetes mellitus insufficiently controlled with metformin.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre study enrolling participants with Type 2 diabetes (n = 484) treated with metformin. Participants were randomized to receive either lixisenatide in a one-step dose increase or a two-step dose increase vs. placebo for 24 weeks, followed by a ≥ 52-week variable double blind period. Primary outcome was HbA1c reduction at week 24.
  
  
  RESULTS
  Lixisenatide one-/two-step once daily significantly improved HbA1c at week 24 compared with placebo (P < 0.0001) and allowed more participants to achieve HbA1c < 53 mmol/mol (< 7.0%) (P ≤ 0.0005). Improvements were observed in fasting plasma glucose (-0.5/-0.6 vs. +0.1 mmol/l; P < 0.001) and body weight (-2.6/-2.7 vs. -1.6 kg; P < 0.005). At week 24, adverse events were reported by 67.7/70.8/65.6% of participants treated with lixisenatide one-/two-step/placebo, respectively--nausea and vomiting being reported most frequently. Symptomatic hypoglycaemia occurred in 1.9/2.5% of participants on one-/two-step lixisenatide and 0.6% with placebo, with no severe episodes. Lixisenatide continued to be efficacious and well tolerated during the variable double-blind extension period of at least 52 weeks.
  
  
  CONCLUSIONS
  Lixisenatide one- or two-step dose-increase regimens significantly improved glycaemic control and decreased body weight over 24 weeks and during a long-term extension period without increasing hypoglycaemia. The study confirmed that tolerability in the one-step group was at least similar to the two-step dose increase, with nausea/vomiting and hypoglycaemia frequency being lower in the one-step regimen.
authors.affiliation: University of Perugia, Perugia, Italy.
authors.forename: G B
authors.initials: GB
authors.lastname: Bolli
authors.forename: M
authors.initials: M
authors.lastname: Munteanu
authors.forename: S
authors.initials: S
authors.lastname: Dotsenko
authors.forename: E
authors.initials: E
authors.lastname: Niemoeller
authors.forename: G
authors.initials: G
authors.lastname: Boka
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Hanefeld
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects*; D010919:Placebos; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D010455:Peptides; D010919:Placebos; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor