{
  "abstract": "Background/Objectives: Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective for body weight reduction, there remains a critical unmet need for complementary strategies that drive selective fat loss and sustain long-term weight reduction. This study aimed to investigate whether Vutiglabridin, a novel oral small-molecule anti-obesity drug, complements GLP-1 RAs to enhance therapeutic efficacy by selectively reducing fat mass and achieving normal body composition.\n\nSubjects/Methods: 6-week-old mice were fed a high-fat diet (60 kcal% fat) for 11 weeks to generate mice with diet-induced obesity (DIO) and then treated with GLP-1 RAs (Semaglutide, Liraglutide, or Exenatide) either alone or in combination with Vutiglabridin for 3–4 weeks.\n\nInterventions/Methods: Body weight, food intake, fat mass, and lean mass were evaluated during treatment. For the drug discontinuation study, mice were administered Vutiglabridin, Semaglutide, or the combination for 4 weeks, after which treatment was withdrawn on Day 28 and body weight regain was monitored for 21 days.\n\nResults: In DIO mice treated with Semaglutide, weight loss attenuated, and body weight was maintained at a constant level after 2 weeks. In contrast, co-administration of Vutiglabridin overcame this attenuation of efficacy, enabling continuous weight reduction and achieving normal body composition. Vutiglabridin also resolved the diminishing weight-loss effect when combined with comparatively less potent appetite-suppressing GLP-1 RAs, including liraglutide and exenatide. In addition to normalizing body composition, Vutiglabridin mitigated the body weight and fat-mass regain that occurs following Semaglutide discontinuation.\n\nConclusions: These findings demonstrate that Vutiglabridin can normalize body composition in combination with multiple GLP-1 RAs, highlighting its potential as a novel therapeutic option for obesity treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Glaceum Inc., Suwon, Republic of Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hyeong Min Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Kamindu Gayashan Marakkalage"
    },
    {
      "affs": [
        0
      ],
      "name": "Sang Hyo Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Soonje Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Jae Ho Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Hyung Soon Park"
    },
    {
      "affs": [
        0
      ],
      "name": "Sang-Ku Yoo",
      "orcid": "0000-0002-2090-4256"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/128d7k2ywj4e2.bib",
  "cited_by": 0,
  "doi": "10.1038/s41366-026-02161-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13722581/",
  "id": "128d7k2ywj4e2",
  "issns": [
    "0307-0565",
    "1476-5497"
  ],
  "landing_url": "https://doi.org/10.1038/s41366-026-02161-9",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2736|Pharmacology and Obesity Treatment"
    ]
  ],
  "openalex": "W4417171833",
  "pdf_url": "https://www.nature.com/articles/s41366-026-02161-9.pdf",
  "pmcid": "PMC13722581",
  "pmid": "42457940",
  "published": "2026-07-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/128d7k2ywj4e2.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:22Z",
      "native_id": "PMC13722581",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41366-026-02161-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Pharmacology and Obesity Treatment",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Vutiglabridin overcomes the GLP-1 RA-associated weight-loss plateau to achieve normal body weight",
  "title_text": "Vutiglabridin overcomes the GLP-1 RA-associated weight-loss plateau to achieve normal body weight",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:22Z",
  "url": "https://research.draconitic.com/paper/128d7k2ywj4e2",
  "venue": "International Journal of Obesity (2005)",
  "versions": []
}