Effect of the once-daily human GLP-1 analogue liraglutide on appetite, energy intake, energy expenditure and gastric emptying in type 2 diabetes

Diabetes Res Clin Pract. 2012 Aug;97(2):258-66. doi: 10.1016/j.diabres.2012.02.016. Epub 2012 Mar 24.

Abstract

Aims: 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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Appetite / drug effects*
  • Australia
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Energy Intake / drug effects*
  • Energy Metabolism / drug effects*
  • Female
  • Gastric Emptying / drug effects*
  • Glucagon-Like Peptide 1 / administration & dosage*
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / pharmacology
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Liraglutide
  • Male
  • Middle Aged
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Obesity / physiopathology
  • Sulfonylurea Compounds / administration & dosage*
  • Sulfonylurea Compounds / pharmacology
  • Young Adult

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • glimepiride
  • Liraglutide
  • Glucagon-Like Peptide 1