Preclinical evaluation and first-in-human phase 1 trial of AZD0186, a novel, oral small molecule glucagon-like peptide-1 receptor agonist

AZD0186, a small molecule glucagon-like peptide-1 receptor agonist, showed a 9.9% reduction in body weight in human glucagon-like peptide-1 receptor mice after 5 days of dosing.

• AZD0186 demonstrated potent activity on the human glucagon-like peptide-1 receptor, with an effective concentration of 0.6 nM.
• Insulin secretion was significantly enhanced in obese nonhuman primates at all three tested dose levels during an intravenous glucose tolerance test.
• In human glucagon-like peptide-1 receptor mice, body weight reduction was observed following oral dosing of 25 mg/kg per day twice a day.
• AZD0186 was well tolerated in healthy participants, with nausea occurring at the highest dose of 150 mg.
• The pharmacokinetics of AZD0186 showed an approximately dose-proportional increase in area under the concentration-time curve across the dose range.
• The median terminal half-life of AZD0186 ranged from 1.95 to 7.58 hours.

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