A randomized phase I study of BI 1820237, a novel neuropeptide Y receptor type 2 agonist, alone or in combination with low‐dose liraglutide in otherwise healthy men with overweight or obesity

Oct 7, 2024Diabetes, obesity & metabolism

Early trial of a new brain receptor activator alone or with low-dose liraglutide in healthy overweight men

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

In a study involving 95 men with increased BMI, drug-related gastrointestinal adverse events were reported by 39.0% of participants receiving the peptidic NPY2R agonist BI 1820237.

Gastrointestinal adverse events were the most common side effects associated with BI 1820237.
The combination of BI 1820237 and low-dose liraglutide did not show differences in tolerability compared to BI 1820237 alone.
Post-dose analysis indicated that BI 1820237 and liraglutide may have additive effects on gastric emptying.
Transient nausea and vomiting were observed in participants receiving higher doses of BI 1820237.

AI simplified

AIMS: Pharmacotherapeutic options for obesity treatment include glucagon-like peptide-1 receptor (GLP-1R) agonists, for example, liraglutide. However, an unmet need remains, particularly in patients with a high body mass index (BMI), as GLP-1R agonists are associated with gastrointestinal adverse events (AEs) and some patients do not respond to treatment. Neuropeptide Y (NPY) and peptide YY bind G-protein-coupled Y receptors and represent attractive targets for modulating bodyweight.

MATERIALS AND METHODS: This first-in-human, three-part, partially blinded phase I study (NCT04903509) investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of the peptidic NPY2R agonist BI 1820237, with/without low-dose liraglutide: part 1 (participants randomized to receive BI 1820237: 0.075-2.4 mg or placebo), part 2 (BI 1820237: 1.2 mg or placebo) and part 3 (BI 1820237: 0.025-1.2 mg + liraglutide 0.6 mg or placebo + liraglutide 0.6 mg). Primary endpoint is the proportion of participants with drug-related AEs. Secondary endpoints are tolerability, PK and PD.

RESULTS: In total, 95 otherwise healthy men with increased BMI (25.0-34.9 kg/m) were randomized. Drug-related AEs, mainly gastrointestinal events, were reported by 39.0% of participants (n = 23) in parts 1 + 2 and 30.6% of participants (n = 11) in part 3; one drug-related AE (11.1%, part 3) was reported in a participant receiving placebo with liraglutide. Post-dose paracetamol PK suggested that BI 1820237 and low-dose liraglutide exhibited additive effects on gastric emptying. 2

CONCLUSIONS: BI 1820237 treatment was associated with transient nausea and vomiting at higher doses. No differences in tolerability were observed when combined with liraglutide; effects on gastric emptying appeared additive.

Full Text

Full text is available at the source.

View full text ↗

A randomized phase I study of BI 1820237, a novel neuropeptide Y receptor type 2 agonist, alone or in combination with low‐dose liraglutide in otherwise healthy men with overweight or obesity

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief