AstraZeneca's New Oral GLP-1 Drug AZD0186 Passes Its First Human Test

Novel oral GLP-1 small molecule AZD0186 showed GLP-1 receptor activation, glucose-stimulated insulin secretion, and weight loss effects in preclinical and Phase 1 human testing.

Qi, Weier et al.·The Journal of pharmacology and experimental therapeutics·2025·Moderate Evidencerct
RPEP-13139RctModerate Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
rct
Evidence
Moderate Evidence
Sample
N=N=79 (phase 1)
Participants
Healthy adults (phase 1); obese nonhuman primates and humanized mice (preclinical)

What This Study Found

AZD0186 activated GLP-1 receptors, stimulated insulin secretion, and reduced weight in preclinical models, with acceptable Phase 1 human safety.

Key Numbers

Doses 5-150 mg tested in humans; dose-dependent GSIS in animals and humans; no serious AEs reported.

How They Did This

Preclinical (cell lines, EndoC-βH5 cells, NHP, hGLP-1R mice) plus first-in-human randomized single ascending dose trial.

Why This Research Matters

Another oral GLP-1 drug entering the pipeline increases competition, which should improve access and reduce costs for patients.

The Bigger Picture

With multiple oral GLP-1 drugs now in Phase 1-3 (oral semaglutide, orforglipron, HDM1002, AZD0186), the competitive landscape is intensifying.

What This Study Doesn't Tell Us

Phase 1 single-dose data only — efficacy, chronic safety, and optimal dosing not yet established.

Questions This Raises

  • ?How does AZD0186 compare to orforglipron in terms of bioavailability and efficacy?
  • ?What differentiates AZD0186's mechanism from other oral GLP-1 small molecules?

Trust & Context

Key Stat:
Phase 1 complete AZD0186 first-in-human SAD trial demonstrates safety and pharmacokinetics for further development
Evidence Grade:
Combined preclinical and Phase 1 data — comprehensive early-stage development package.
Study Age:
Published in 2025, part of the accelerating oral GLP-1 drug development race.
Original Title:
Preclinical evaluation and first-in-human phase 1 trial of AZD0186, a novel, oral small molecule glucagon-like peptide-1 receptor agonist.
Published In:
The Journal of pharmacology and experimental therapeutics, 392(10), 103683 (2025)
Database ID:
RPEP-13139

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

What is AZD0186?

A new oral GLP-1 drug from AstraZeneca designed to be a convenient pill form alternative to injectable GLP-1 medications for diabetes and obesity.

How many oral GLP-1 pills are being developed?

Several, including oral semaglutide (approved), orforglipron, HDM1002, and AZD0186 — competition is expanding patient options.

Read More on RethinkPeptides

Cite This Study

RPEP-13139·https://rethinkpeptides.com/research/RPEP-13139

APA

Qi, Weier; Boca, Simina M; Boianelli, Alessandro; Fredberg, Monica; Lundqvist, Sara; Davies, Graeme; Field, Joss; Brighton, Cheryl A; Snijder, Arjan; Grundevik, Pernilla; Eckernäs, Daniel; Träff, Annika Maria; Polla, Magnus; Pettersen, Daniel; Omar, Sami; Hansen, Lars; Janzén, David; Melin, Johanna; van Zuydam, Natalie; Logue, Jennifer; Wallenius, Kristina. (2025). Preclinical evaluation and first-in-human phase 1 trial of AZD0186, a novel, oral small molecule glucagon-like peptide-1 receptor agonist.. The Journal of pharmacology and experimental therapeutics, 392(10), 103683. https://doi.org/10.1016/j.jpet.2025.103683

MLA

Qi, Weier, et al. "Preclinical evaluation and first-in-human phase 1 trial of AZD0186, a novel, oral small molecule glucagon-like peptide-1 receptor agonist.." The Journal of pharmacology and experimental therapeutics, 2025. https://doi.org/10.1016/j.jpet.2025.103683

RethinkPeptides

RethinkPeptides Research Database. "Preclinical evaluation and first-in-human phase 1 trial of A..." RPEP-13139. Retrieved from https://rethinkpeptides.com/research/qi-2025-preclinical-evaluation-and-firstinhuman

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.