Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults

Int J Obes (Lond). 2014 Jun;38(6):784-93. doi: 10.1038/ijo.2013.162. Epub 2013 Sep 3.

Abstract

Introduction: Mechanisms for liraglutide-induced weight loss are poorly understood.

Objective: We investigated the effects of liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese non-diabetic individuals.

Design: Participants (N=49, 18-75 years, body mass index: 30-40 kg m(-2)) were randomized to two of three treatments: liraglutide 1.8 mg, 3.0 mg, or placebo in a double-blind, incomplete crossover trial. After 5 weeks, 24-h energy expenditure (EE) and substrate oxidation were measured in a respiratory chamber. Gastric emptying (acetaminophen absorption method), glycemic parameters and appetite were assessed during a 5-h meal test. Ad libitum energy intake during a subsequent lunch was also assessed.

Results: Five-hour gastric emptying (AUC(0-300 min)) was found to be equivalent for liraglutide 1.8 versus 3.0 mg (primary end point), and for both liraglutide doses versus placebo, as 90% confidence intervals for the estimated treatment ratios were contained within the prespecified interval (0.80-1.25). However, 1-h gastric emptying was 23% lower than placebo with liraglutide 3.0 mg (P=0.007), and a nonsignificant 13% lower than placebo with liraglutide 1.8 mg (P=0.14). Both liraglutide doses similarly reduced fasting glucose (0.5-0.6 mmol l(-1) versus placebo, P<0.0001), glucose Cmax and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC(0-300 min) (by ∼26% versus placebo, P=0.02). Glucagon iAUC(0-300 min) decreased by ∼30%, and iAUC(0-60 min) for insulin and C-peptide was ∼20% lower with both liraglutide doses versus placebo. Liraglutide doses similarly increased mean postprandial satiety and fullness ratings, reduced hunger and prospective food consumption and decreased ad libitum energy intake by ∼16%. Liraglutide-associated reductions in EE were partly explained by a decrease in body weight. A relative shift toward increased fat and reduced carbohydrate oxidation was observed with liraglutide. Clinicaltrials.gov ID:NCT00978393.

Funding: Novo Nordisk.

Conclusion: Gastric emptying AUC(0-300 min) was equivalent for liraglutide 1.8 and 3.0 mg, and for liraglutide versus placebo, whereas reductions in 1-h gastric emptying of 23% with liraglutide 3.0 mg and 13% with 1.8 mg versus placebo were observed. Liraglutide 3.0 mg improved postprandial glycemia to a greater extent than liraglutide 1.8 mg. Liraglutide-induced weight loss appears to be mediated by reduced appetite and energy intake rather than increased EE.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Appetite / drug effects*
  • Blood Glucose / drug effects
  • Body Mass Index
  • Body Weight / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Energy Intake / drug effects
  • Energy Metabolism / drug effects
  • Female
  • Gastric Emptying / drug effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glycated Hemoglobin A / drug effects*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Liraglutide
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy*
  • Satiation
  • Treatment Outcome
  • Weight Loss / drug effects*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Liraglutide
  • Glucagon-Like Peptide 1

Associated data

  • ClinicalTrials.gov/NCT00978393