title: Effect of the once-daily human GLP-1 analogue liraglutide on appetite, energy intake, energy expenditure and gastric emptying in type 2 diabetes.
abstract: OBJECTIVE
  Liraglutide reduces bodyweight in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the mechanisms underlying this effect.
  
  
  METHODS
  The comparative effects of liraglutide, glimepiride and placebo on energy intake, appetite, nausea, gastric emptying, antral distension, bodyweight, gastrointestinal hormones, fasting plasma glucose and resting energy expenditure (REE), were assessed in subjects with T2DM randomised to treatment A (liraglutide-placebo), B (placebo-glimepiride) or C (glimepiride-liraglutide). Assessments were performed at the end of each 4-week treatment period.
  
  
  RESULTS
  Energy intake was less (NS) with liraglutide vs placebo and glimepiride, and 24-h REE was higher (NS) with liraglutide vs placebo and glimepiride. Fasting hunger was less (p=0.01) with liraglutide vs placebo and glimepiride, and meal duration was shorter with liraglutide (p=0.002) vs placebo. Paracetamol AUC(0-60 min) and C(max) were less (p<0.01) and fasting peptide YY was lower (p ≤ 0.001) after liraglutide vs placebo and glimepiride. Bodyweight reductions of 1.3 and 2.0 kg were observed with liraglutide vs placebo and glimepiride (p<0.001). There were no differences on antral distension, nausea, or other gastro-intestinal hormones.
  
  
  CONCLUSIONS
  Liraglutide caused decreased gastric emptying and increased reduction in bodyweight. The mechanisms of the liraglutide-induced weight-loss may involve a combined effect on energy intake and energy expenditure.
authors.affiliation: University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, Australia. michael.horowitz@adelaide.edu.au
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.forename: Anne
authors.initials: A
authors.lastname: Flint
authors.forename: Karen L
authors.initials: KL
authors.lastname: Jones
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hindsberger
authors.forename: Mads F
authors.initials: MF
authors.lastname: Rasmussen
authors.forename: Christoph
authors.initials: C
authors.lastname: Kapitza
authors.forename: Selena
authors.initials: S
authors.lastname: Doran
authors.forename: Thomas
authors.initials: T
authors.lastname: Jax
authors.forename: Milan
authors.initials: M
authors.lastname: Zdravkovic
authors.forename: Ian M
authors.initials: IM
authors.lastname: Chapman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001066:Appetite / Q000187:drug effects*; D001315:Australia; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002149:Energy Intake / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1