title: Liraglutide's safety, tolerability, pharmacokinetics, and pharmacodynamics in pediatric type 2 diabetes: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  The prevalence of type 2 diabetes (T2D) in youth is increasing. Treatment options beyond metformin and insulin are needed. The safety, tolerability, pharmacokinetics, and pharmacodynamics of liraglutide once daily in youth (10-17 years old) with T2D were investigated in a randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  Youth treated with diet/exercise alone or with metformin and having a hemoglobin A1c (HbA1c) level of 6.5-11% were randomized to liraglutide (n=14) or placebo (n=7). Starting at 0.3 mg/day, doses were escalated weekly to 0.6, 0.9, 1.2, and 1.8 mg/day (or placebo equivalent) for 5 weeks.
  
  
  RESULTS
  Nineteen participants completed the trial. Baseline characteristics were similar between groups, with mean (SD) values for age of 14.8 (2.2) years, weight of 113.2 (35.6) kg (range, 57-214 kg), diabetes duration of 1.7 (1.4) years, and HbA1c level of 8.1% (1.2%). No serious adverse events (AEs), including severe hypoglycemia, occurred. Transient gastrointestinal AEs were most common at lower liraglutide doses during dose escalation. No significant changes in safety and tolerability parameters occurred. There was no evidence of pancreatitis or lipase elevations above three times the upper normal limit; calcitonin levels remained within the normal range. For liraglutide 1.8 mg, mean half-life was 12 h, and clearance was 1.7 L/h. After 5 weeks, the decline in HbA1c level was greater with liraglutide versus placebo (-0.86 vs. 0.04%, P=0.0007), whereas mean body weight remained stable (-0.50 vs. -0.54 kg, P=0.9703).
  
  
  CONCLUSIONS
  Liraglutide was well tolerated in youth with T2D, with safety, tolerability, and pharmacokinetic profiles similar to profiles in adults.
authors.affiliation: 1 Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
authors.forename: David J
authors.initials: DJ
authors.lastname: Klein
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.forename: D J
authors.initials: DJ
authors.lastname: Chatterjee
authors.forename: Lisbeth V
authors.initials: LV
authors.lastname: Jacobsen
authors.forename: Paula M
authors.initials: PM
authors.lastname: Hale
authors.forename: Silva
authors.initials: S
authors.lastname: Arslanian
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001530:Belgium / Q000453:epidemiology; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000069450:Liraglutide; D063766:Pediatric Obesity / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D015995:Prevalence; D017524:Slovenia / Q000453:epidemiology; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; C517652:hemoglobin A1c protein, human