title: Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono).
abstract: OBJECTIVE
  To assess efficacy and safety of lixisenatide monotherapy in type 2 diabetes.
  
  
  METHODS
  Randomized, double-blind, 12-week study of 361 patients not on glucose-lowering therapy (HbA(1c) 7-10%) allocated to one of four once-daily subcutaneous dose increase regimens: lixisenatide 2-step (10 μg for 1 week, 15 μg for 1 week, and then 20 μg; n = 120), lixisenatide 1-step (10 μg for 2 weeks and then 20 μg; n = 119), placebo 2-step (n = 61), or placebo 1-step (n = 61) (placebo groups were combined for analyses). Primary end point was HbA(1c) change from baseline to week 12.
  
  
  RESULTS
  Once-daily lixisenatide significantly improved HbA(1c) (mean baseline 8.0%) in both groups (least squares mean change vs. placebo: -0.54% for 2-step, -0.66% for 1-step; P < 0.0001). Significantly more lixisenatide patients achieved HbA(1c) <7.0% (52.2% 2-step, 46.5% 1-step) and ≤ 6.5% (31.9% 2-step, 25.4% 1-step) versus placebo (26.8% and 12.5%, respectively; P < 0.01). Lixisenatide led to marked significant improvements of 2-h postprandial glucose levels and blood glucose excursions measured during a standardized breakfast test. A significant decrease in fasting plasma glucose was observed in both lixisenatide groups versus placebo. Mean decreases in body weight (∼2 kg) were observed in all groups. The most common adverse events were gastrointestinal-nausea was the most frequent (lixisenatide 23% overall, placebo 4.1%). Symptomatic hypoglycemia occurred in 1.7% of lixisenatide and 1.6% of placebo patients, with no severe episodes. Safety/tolerability was similar for the two dose regimens.
  
  
  CONCLUSIONS
  Once-daily lixisenatide monotherapy significantly improved glycemic control with a pronounced postprandial effect (75% reduction in glucose excursion) and was safe and well tolerated in type 2 diabetes.
authors.affiliation: Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, USA. vfonseca@tulane.edu
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Fonseca
authors.forename: Ricardo
authors.initials: R
authors.lastname: Alvarado-Ruiz
authors.forename: Denis
authors.initials: D
authors.lastname: Raccah
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; D001786:Blood Glucose / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring; D001794:Blood Pressure; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D019518:Postprandial Period; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; C517652:hemoglobin A1c protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor