{
  "abstract": "Insulin resistance (IR) and body weight are closely linked in type 2 diabetes (T2D), so their molecular correlates are hard to separate in observational data. Pan-PPAR agonism offers a test, because it improves insulin sensitivity while body weight increases. In the ChiHOPE cohort of 835 T2D patients from two randomized phase 3 trials of chiglitazar, 53% of chiglitazar-treated patients with HOMA-IR-defined IR at baseline no longer met the IR threshold after treatment, compared with 29% with placebo and 32% with sitagliptin, while BMI rose. We integrated plasma metabolomics and proteomics into a molecular estimate of HOMA-IR. It outperformed routine clinical measures, disagreed with HOMA-IR classification in 27% of patients, and identified adverse lipid, liver and inflammatory profiles within each HOMA-IR class. With chiglitazar, the molecular estimate fell despite weight gain, with lower proteoglycan 4 and higher glutamine and glycine. Circulating markers of IR can therefore improve without weight loss.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Department of Pathology, Zhongshan Hospital, Fudan University,"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 38,
  "authors": [
    {
      "name": "Z. Cao"
    },
    {
      "name": "J. Li"
    },
    {
      "name": "N. Zhang"
    },
    {
      "name": "H. Chen"
    },
    {
      "name": "D. Pan"
    },
    {
      "name": "Q. Chen"
    },
    {
      "name": "Y. Mai"
    },
    {
      "name": "X. Yao"
    },
    {
      "name": "S. Sun"
    },
    {
      "name": "Y. Liu"
    },
    {
      "name": "W. Hou"
    },
    {
      "name": "Y. Yu"
    },
    {
      "name": "Y. An"
    },
    {
      "name": "Z. Yuan"
    },
    {
      "name": "J. Tan"
    },
    {
      "name": "X. Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Zheng"
    },
    {
      "name": "H. Wu"
    },
    {
      "name": "J. Wang"
    },
    {
      "name": "J. Chang"
    },
    {
      "name": "C. Ding"
    },
    {
      "name": "Q. Huang"
    },
    {
      "name": "Q. Wang"
    },
    {
      "name": "B. Jiang"
    },
    {
      "name": "S. Wang"
    },
    {
      "name": "Q. Peng"
    },
    {
      "name": "W. Li"
    },
    {
      "name": "D. Pan"
    },
    {
      "name": "Y. Wang"
    },
    {
      "name": "T. Xu"
    },
    {
      "name": "L. Ji"
    },
    {
      "name": "W. Jia"
    },
    {
      "name": "L. Jin"
    },
    {
      "name": "Z. Ning"
    },
    {
      "name": "A. Vidal-Puig"
    },
    {
      "name": "X. Lu"
    },
    {
      "name": "L. Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Zheng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7fv1wmb7yezcv.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.06.26367120",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.11.06.26367120v1.full",
  "id": "7fv1wmb7yezcv",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.11.06.26367120v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "endocrinology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.11.06.26367120v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7fv1wmb7yezcv.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T00:20:54Z",
      "native_id": "10.64898/2026.11.06.26367120",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.11.06.26367120v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:endocrinology",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Insulin resistance reverses despite weight gain with pan-PPAR agonism, revealing its plasma molecular correlates in type 2 diabetes",
  "title_text": "Insulin resistance reverses despite weight gain with pan-PPAR agonism, revealing its plasma molecular correlates in type 2 diabetes",
  "type": "preprint",
  "updated_at": "2026-11-09T12:20:30Z",
  "url": "https://research.draconitic.com/paper/7fv1wmb7yezcv",
  "venue": "medRxiv",
  "versions": []
}