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Study · Animal study (in vivo) · mouse · 2026

1 result

ARD-101, a gut-restricted TAS2R agonist, reduces hunger in adults and promotes weight loss in DIO mice with DPP-4 inhibition.

Zheng Z, Pettus JH, Warner A, Jones B, Pugsley M, Stege J, Hirakawa B, Jaiman M, Tolentino J, Lee TL, Kieffer TJ

Molecular metabolism14 Mar 2026Cited by 3 (Europe PMC)

PMID41833222 (opens in a new tab)PMCIDPMC12990342 (opens in a new tab)DOI10.1016/j.molmet.2026.102340 (opens in a new tab)PepBankPUB-41833222
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Summary

ObjectivesObesity management has limited oral pharmacotherapies. Bitter taste receptor (TAS2R) agonists may modulate hunger, satiety, and metabolism via gut-brain signaling. We evaluated denatonium acetate (DA), a gut-restricted TAS2R agonist, across preclinical and clinical settings, and explored its combination with sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor).MethodsIn mice transitioned to high-fat diet (HFD) or established with diet-induced obesity (DIO), we tested oral DA (20-80 mg/kg twice daily or 75 mg/kg once daily), a sitagliptin-formulated HFD, the combination, and subcutaneous tirzepatide, including a post-tirzepatide discontinuation phase, to assess weight trajectories and metabolic benefits. In randomized, placebo-controlled clinical studies, ARD-101 (oral DA) was evaluated in adults with obesity (200 mg twice daily for 28 days) and in healthy participants (single 800 mg).ResultsIn mice transitioned to HFD, DA reduced weight gain (up to 43.1%), decreased food intake, and improved glucose and lipid measures. In DIO mice, once-daily DA or sitagliptin-HFD prevented weight gain; the combination reduced body weight (-18.8%) with metabolic benefits. In a separate DIO mouse study, tirzepatide reduced weight by 23.7%. Following tirzepatide discontinuation, switching to DA plus sitagliptin-HFD limited weight regain comparable to continued tirzepatide. In adults with obesity, ARD-101 reduced weight versus placebo by 0.8 kg at Day 28 and 1.3 kg at end-of-study and decreased hunger and food cravings. It also altered gut hormone levels in healthy participants.ConclusionsGut-restricted TAS2R agonism warrants further study for hyperphagia in Prader-Willi syndrome, and in combination with DPP-4 inhibition for obesity.ClinicaltrialsGov numberNCT05121441.Integrated research application system (iras) number1011885.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

1 result from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In diet-induced obese mice, subcutaneous tirzepatide reduced body weight by 23.7%.

    In plain wordsIn mice with diet-induced obesity, tirzepatide lowered body weight by 23.7%.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight reduction in DIO mice
    Study

    mousen: not reported in source

    diet-induced obesity (DIO) mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · subcutaneousAs given in this study (mouse).

    Measurements

    body weight reduction
    23.7%
    DIO mice

    Source sentences

    Summary
    In a separate DIO mouse study, tirzepatide reduced weight by 23.7%.
    1 context sentence
    Summary · context
    In mice transitioned to high-fat diet (HFD) or established with diet-induced obesity (DIO), we tested oral DA (20-80 mg/kg twice daily or 75 mg/kg once daily), a sitagliptin-formulated HFD, the combination, and subcutaneous tirzepatide

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    12 Oct 2026, 12:10 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:07 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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