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.
Phase 1 completeAZD0186 first-in-human SAD trial demonstrates safety and pharmacokinetics for further development
What the researchers found
AZD0186 activated GLP-1 receptors, stimulated insulin secretion, and reduced weight in preclinical models, with acceptable Phase 1 human safety.
Why it matters
Another oral GLP-1 drug entering the pipeline increases competition, which should improve access and reduce costs for patients.
The numbers in context
Doses 5-150 mg tested in humans; dose-dependent GSIS in animals and humans; no serious AEs reported.
How the study worked
Preclinical (cell lines, EndoC-βH5 cells, NHP, hGLP-1R mice) plus first-in-human randomized single ascending dose trial.
Who was studied
Healthy adults (phase 1); obese nonhuman primates and humanized mice (preclinical)
What this study cannot tell us
Phase 1 single-dose data only — efficacy, chronic safety, and optimal dosing not yet established.
How to read the evidence
Combined preclinical and Phase 1 data — comprehensive early-stage development package.
When this study was published
Published in 2025, part of the accelerating oral GLP-1 drug development race.
The bigger picture
With multiple oral GLP-1 drugs now in Phase 1-3 (oral semaglutide, orforglipron, HDM1002, AZD0186), the competitive landscape is intensifying.
Questions still open
- How does AZD0186 compare to orforglipron in terms of bioavailability and efficacy?
- What differentiates AZD0186's mechanism from other oral GLP-1 small molecules?
Common questions
What is AZD0186?
How many oral GLP-1 pills are being developed?
Read the original research
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
Citation
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