Journal Article

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

Jensen, C B, Sloth, B, Blaak, E E, van Can, J, Saris, W H M, Flint, A

2014

Overview

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 C max 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/443/319 / 692/699/2743/393 / 692/700/2817 / Absorption / Adolescent / Adult / Aged / Appetite / Appetite - drug effects / Biological and medical sciences / Blood Glucose - drug effects / Body Mass Index / Body weight / Body Weight - drug effects / Cross-Over Studies / Diabetes / Diabetes. Impaired glucose tolerance / Double-Blind Method / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Energy / Energy Intake - drug effects / Energy Metabolism - drug effects / Epidemiology / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Gastric Emptying - drug effects / Gastrointestinal system / Glucagon / Glucagon-Like Peptide 1 - analogs & derivatives / Glucagon-Like Peptide 1 - therapeutic use / Glucose / Glycated Hemoglobin A - drug effects / Health Promotion and Disease Prevention / Humans / Hunger / Hypoglycemic Agents - therapeutic use / Insulin / Internal Medicine / Investigations / Liraglutide / Male / Medical sciences / Medicine / Medicine & Public Health / Metabolic Diseases / Metabolism / Middle Aged / Motility / Nutrition / Obesity / Obesity - complications / Obesity - drug therapy / Oral administration / Original / original-article / Oxidation / Patient outcomes / Peptides / Physiological aspects / Physiological research / Public Health / Satiation / Toxicology / Treatment Outcome / Weight control / Weight Loss - drug effects