title: Liraglutide 3.0 mg for Weight Management: A Population Pharmacokinetic Analysis.
abstract: This analysis used a population pharmacokinetic approach to identify covariates that influence plasma exposure of liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist approved for weight management in overweight and obese individuals.
  
  
  
  Samples for pharmacokinetic analysis were drawn at weeks 2, 12 and 28 of the phase IIIa SCALE Obesity and Prediabetes (N = 2339) and SCALE Diabetes (N = 584) trials. Dose proportionality of liraglutide in obese subjects was investigated using data from a phase II dose-finding study (N = 331).
  
  
  
  Dose-proportional exposure of liraglutide up to and including 3.0 mg was confirmed. Body weight and sex influenced exposure of liraglutide 3.0 mg, while age ≥70 years, race, ethnicity and baseline glycaemic status did not. Compared with a reference subject weighing 100 kg, exposure of liraglutide 3.0 mg was 44 % lower for a subject weighing 234 kg (90 % CI 41-47), 41 % higher for a subject weighing 60 kg (90 % CI 37-46), and 32 % higher (90 % CI 28-35) in females than males with the same body weight. Neither injection site nor renal function significantly influenced exposure of liraglutide 3.0 mg (post hoc analysis).
  
  
  
  Population pharmacokinetics of liraglutide up to and including 3.0 mg daily in overweight and obese adults demonstrated dose-proportional exposure, and limited effect of covariates other than sex and body weight. These findings were similar to those previously observed with liraglutide up to 1.8 mg in subjects with type 2 diabetes mellitus. Further analysis of exposure-response relationship and its effect on dose requirements is addressed in a separate publication.
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark. RUVO@novonordisk.com.
authors.forename: Rune V
authors.initials: RV
authors.lastname: Overgaard
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark.
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Petri
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark.
authors.forename: Lisbeth V
authors.initials: LV
authors.lastname: Jacobsen
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Jensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069450:Liraglutide / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000188:drug therapy* / Q000453:epidemiology; D050177:Overweight / Q000188:drug therapy / Q000453:epidemiology; D011236:Prediabetic State / Q000188:drug therapy* / Q000453:epidemiology; D012737:Sex Factors; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1