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Adipose Tissue_Appetite_and Obesity

SAT-670 - Tirzepatide Effects on Insulin Resistance and Β-Cell Function: A Systematic Review and Meta-Analysis

Saturday, June 13, 2026
9:30 AM - 4:30 PM CT
Location: ENDOExpo; Poster Floor

    Abstract Poster Presenter(s)

  • Dimitrios Raptis, MD MSc

    MD
    Albert Einstein College of Medicine/New York City Health and Hospitals/Jacobi/North Central Bronx
    Bronx, NY, United States

    • Senior Author/Primary Investigator(s)

  • Dimitrios Raptis, MD MSc

    MD
    Albert Einstein College of Medicine/New York City Health and Hospitals/Jacobi/North Central Bronx
    Bronx, NY, United States

    • Co-Author(s)

  • TP

    Theodoros Papamichalis, MD MSc

    MD
    251 Hellenic Air Force General Hospital/Department of Medicine, Athens, Greece
    Athens, Greece

  • PT

    Panagiotis Theodoropoulos, MD

    MD
    Albert Einstein College of Medicine/New York City Health and Hospitals/Jacobi Medical Center
    Bronx NY, NY, United States

  • MK

    Michail Kladas, MD

    Albert Einstein College of Medicine/New York City Health and Hospitals/Jacobi/North Central Bronx

Glucagon-like peptide-1-based therapies have been widely evaluated for their effects on insulin sensitivity and β-cell function using HOMA-derived indices. However, despite the growing clinical use of the dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist tirzepatide, the effects of tirzepatide on insulin resistance and β-cell function have not been systematically synthesized using HOMA2-derived indices.

We performed a systematic literature search in PubMed, the Cochrane Library, and ClinicalTrials.gov through December 13, 2025 and identified 221 records, of which three studies met inclusion criteria by reporting changes in HOMA2-B and/or HOMA2-IR following tirzepatide therapy. Tirzepatide doses ranged from 1 to 15 mg administered once weekly. Random-effects meta-analyses were conducted using baseline to follow-up changes. Eight study arms contributed data for HOMA2-B and five for HOMA2-IR.

Tirzepatide treatment was associated with a significant improvement in β-cell function, with a pooled weighted mean difference in HOMA2-B of 35.32 (95% CI 25.10 to 45.54; p< 0.0001). In contrast, no significant change in insulin resistance was observed, with a pooled weighted mean difference in HOMA2-IR of -0.13 (95% CI -0.50 to 0.24; p=0.39).

This systematic review and meta-analysis suggests that tirzepatide preferentially improves β-cell function without a corresponding reduction in insulin resistance. Given the limited number of eligible studies, further trials with standardized assessments of insulin sensitivity and β-cell function are warranted to confirm these findings and clarify underlying mechanisms.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*