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/m2) 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.

Original languageEnglish
JournalInternational journal of obesity (2005)
Issue number11
Pages (from-to)2058-2062
Number of pages5
Publication statusPublished - Nov 2022


  • Adult
  • Alanine/therapeutic use
  • Amino Acids
  • Diabetes Mellitus, Type 2/metabolism
  • Glucagon
  • Glucagon-Like Peptide-1 Receptor/agonists
  • Humans
  • Hypoglycemic Agents/pharmacology
  • Insulin/therapeutic use
  • Liraglutide/pharmacology
  • Liver/metabolism
  • Male
  • Middle Aged
  • Overweight/drug therapy


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