Novel Oral Antiobesity Drug Shown to Reduce Body Weight by up to 13% in First-In-Human Study

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Amycretin (Novo Nordisk), a novel oral antiobesity medication, was safe and well tolerated and significantly reduced body weight compared with placebo at 12 weeks in individuals with obesity and without diabetes, findings from a first-in-human study show. The data were presented at the 60th Annual Meeting of the European Association for the Study of Diabetes (EASD) 2024, held in Madrid, Spain, from September 10-13, 2024.

Amycretin is a first-of-its-kind, protein-based unimolecular amylin and glucagon-like peptide-1 (GLP-1) receptor agonist coagonist that is being explored as a once-daily oral alternative to subcutaneous injectable antiobesity medications in persons with overweight or obesity, according to the study abstract.

Data from the phase 1 clinical trial showed that participants who received amycretin 50 mg had a 10.4% reduction in body weight, on average, between baseline and week 12, while those who received amycretin 2x50 mg (the maximum dose tested) had a mean body weight reduction of 13.1%. In comparison, persons in the placebo group had a 1.1% reduction in body weight during the same period (P < .001 for both doses). Inclusion in the study required a body mass index (BMI) of 25.0 to 39.9 kg/m².

With regards to the study’s primary endpoint, treatment-emergent adverse events (AEs), researchers did not observe any significant safety issues related to amycretin. The majority of AEs reported were mild-to-moderate in severity and related to gastrointestinal discomfort (ie, nausea, vomiting) and decreased appetite. In addition, investigators noted that the AEs reported in the study “occurred in a dose-proportional manner,” with low tolerability for dose levels more than 18 mg when amycretin was given as a single dose and more than 12 mg when it was administered for 10 consecutive days. When stepwise dose escalation was introduced, however, all tested dose levels up to and including amycretin 2x50 mg demonstrated acceptable safety and tolerability profiles.

Another key finding was that at the end of the study period, weight loss had not reached a plateau for participants in the amycretin group, indicating “the possibility of achieving further weight reductions with extended treatment,” wrote researchers.

In the single-center, placebo-controlled, double-blinded study, participants were randomly assigned to receive once-daily oral amycretin (n=95) or placebo (n=29) for up to 12 weeks. The amycretin arm consisted of 3 dose parts: single-ascending dose (increasing from 1 mg to 25 mg), 10-day multiple-ascending doses (3 mg to 12 mg), and 12-week multiple-ascending doses (stepwise dose escalation, from 3 mg up to a final dose of 2x50 mg).

“The results underscore the promising potential of amycretin as an anti-obesity medication and may pave the way for a novel patient-centered weight-management option,” authors concluded. “Investigations of amycretin in larger and longer studies are being planned to fully assess its efficacy and safety profile.”

Reference: Gasiorek A, Kirkeby K, Toubro S, et al. Safety, tolerability and weight reduction findings of oral amycretin: A novel amylin and glucagon-like peptide-1 receptor co-agonist, in a first-in-human study. Abstract presented at EASD 2024; September 10-13, 2024. Madrid, Spain.