Four weeks treatment with the GLP-1 receptor analogue liraglutide lowers liver fat and concomitantly circulating glucagon in individuals with overweight

• Published in: International Journal of Obesity Vol. 46; no. 11; pp. 2058 - 2062
• Main Authors: Svane, Maria S., Johannesen, Helle H., Hansen, Adam E., Martinussen, Christoffer, Bojsen-Møller, Kirstine N., Hansen, Martin Lundsgaard, Deacon, Carolyn F., Keller, Sune H., Klausen, Thomas L., Loft, Annika, Kjaer, Andreas, Löfgren, Johan, Madsbad, Sten, Holst, Jens J., Wewer Albrechtsen, Nicolai J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2022; Nature Publishing Group
• Subjects: 59/36; 59/57; 692/163/2743/393; 692/699/2743/2037; Alanine; Amino acids; Antidiabetics; Body weight; Body weight loss; Brief Communication; Diabetes; Diabetes mellitus; Dosage; Epidemiology; Glucagon; Glucagon-like peptide 1; Health Promotion and Disease Prevention; Insulin; Insulin resistance; Internal Medicine; Liver; Markers; Medicine; Medicine & Public Health; Metabolic Diseases; Overweight; Public Health; Receptors; Titration; Weight loss
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-022-01207-y

We investigated the effect of pharmacologically induced weight loss on markers of glucagon resistance in individuals with overweight during treatment with the glucagon-like peptide-1 receptor agonist liraglutide. We performed an open-label study in 14 men with overweight (age 38 ± 11 years, BMI 32 ± 4 kg/m 2 ) without simultaneously diabetes. Subjects were treated with liraglutide, initiated and titrated with 0.6 mg/day/week to reach the final dose of 3.0 mg/day. Subjects were examined at baseline, during titration (Week 4), after 2 weeks of steady state (Week 6) of final dosing of liraglutide and 3 weeks after discontinuation of liraglutide (follow-up). Study participants lost 3.3 ± 1.9 kg (3%) total body weight during the first 4 weeks of treatment with liraglutide. Simultaneously, liver fat content decreased from 12.4 ± 11.6% to 10.2 ± 11.1%, p  = 0.025, whereas fat content in the spleen and subcutaneous tissue was unaltered. Markers of glucagon resistance, including plasma glucagon and the glucagon-alanine-index, also decreased significantly during treatment, but total and individual plasma amino acid concentrations did not. Insulin resistance (HOMA-IR) was unchanged during treatment, whereas insulin clearance increased. Treatment with the GLP-1 receptor analogue liraglutide decreased liver fat content, and simultaneously attenuated glucagon concentrations and the glucagon-alanine index in individuals with overweight without diabetes.