Evidence map›Paper›PMID 41833222›Full record

Trial reportMolecular metabolism2026

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

Zhenhuan Zheng, Jeremy H Pettus, Alexa Warner, Bryan Jones, Megan Pugsley, Justin Stege, Brad Hirakawa, Manasi Jaiman, Jerlyn Tolentino, Tien-Li Lee and 1 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05121441 (A Phase 2, Placebo-Controlled, Randomized, Blinded Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of ARD-101 in Adults With Obesity), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05121441 phase2completednot on this map

A Phase 2, Placebo-Controlled, Randomized, Blinded Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of ARD-101 in Adults With Obesity

TypeinterventionalSponsorAardvark Therapeutics, Inc.Ran2021 to 2022Enrolled20ConditionsObesityArmsARD-101, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Zhenhuan ZhengAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA.
Jeremy H PettusDivision of Endocrinology, Altman Clinical and Translational Research Institute (ACTRI), University of California, San Diego, 9452 Medical Center Drive L1W-515, La Jolla, CA, 92037, USA.
Alexa WarnerAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA.
Bryan JonesAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA.
Megan PugsleyAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA.
Justin StegeAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA.
Brad HirakawaAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA.
Manasi JaimanAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA.
Jerlyn TolentinoAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA.
Tien-Li LeeAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA.
Timothy J KiefferAardvark Therapeutics, 4370 La Jolla Village Drive, Suite 1050, San Diego, CA, 92122, USA; Life Sciences Institute, Department of Cellular and Physiological Sciences, Department of Surgery, School of Biomedical Engineering, University of British Columbia, Vancouver, BC, V6T1Z3, Canada. Electronic address: tim.kieffer@aardvarktherapeutics.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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. CLINICALTRIALS: GOV NUMBER: NCT05121441. INTEGRATED RESEARCH APPLICATION SYSTEM (IRAS) NUMBER: 1011885.

Indexed as

Dipeptidyl-Peptidase IV InhibitorsHungerObesityReceptors, G-Protein-CoupledWeight LossAdultAnimalsAnti-Obesity AgentsDiet, High-FatFemaleHumansMaleMiceMice, Inbred C57BLMiddle AgedSitagliptin PhosphateAnti-Obesity AgentsDipeptidyl-Peptidase IV InhibitorsReceptors, G-Protein-CoupledSitagliptin PhosphateTirzepatideDenatonium acetateDiet-induced obese miceHunger scoreObesityTAS2R agonist

Identifiers

PMID41833222
PMCPMC12990342

What Socratic holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.