Studying the Influence of LEAP2 on Integrated Endocrine Control of Eating During Semaglutide Treatment

What this study is testing ClinicalTrials.gov NCT07171723 ↗

Description as written by the study sponsor.

This clinical study investigates how blocking the hunger-related ghrelin receptor affects appetite and metabolism in individuals with obesity who are treated with semaglutide (a GLP-1 receptor agonist). LEAP2, a naturally occurring hormone that inhibits the ghrelin receptor, is used as the investigational compound. The objective of the study is to clarify how the ghrelin system functions when appetite is suppressed by semaglutide treatment. Participants will receive either LEAP2 or placebo during two experimental visits in a randomized, double-blind, crossover design. The investigators will assess food intake, appetite sensations, glucose metabolism, and hormonal responses. By examining the interaction between semaglutide and ghrelin signaling, the study aims to improve understanding of how multiple appetite-regulating systems interact and whether additional hunger signals remain active during GLP-1 treatment. The findings may inform the development of future treatments for individuals with obesity.

Treatments tested

• Liver-Expressed Antimicrobial Peptide 2 (LEAP2) Biologic

  Continuous intravenous infusion of LEAP2 (Liver-Expressed Antimicrobial Peptide 2), an endogenous inverse agonist and competitive antagonist of the ghrelin receptor (GHSR), administered at 40 pmol/kg/min for 6 hours. LEAP2 inhibits ghrelin-mediated signaling involved in hunger regulation, gastric motility, and growth hormone secretion. This intervention enables investigation of the physiological relevance of ghrelin receptor activity during semaglutide-induced appetite suppression

• Placebo (saline) Other

  Continuous intravenous infusion of isotonic saline (0.9% sodium chloride) for 6 hours. This placebo comparator is used to match the volume, rate, and duration of the active intervention (LEAP2) in a randomized, double-blind, crossover design. The placebo enables assessment of the physiological effects of ghrelin receptor blockade by LEAP2 in individuals with obesity treated with semaglutide