RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

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

Effects of Antagonizing the Ghrelin Receptor in Individuals With Obesity on Treatment With Semaglutide

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - Age between 18 and 65 years old - Body mass index (BMI) above ≥ 25 kg/m2 - Ongoing semaglutide treatment with a stable dose of ≥ 1 mg once weekly for a minimum of 3 months prior to inclusion - Weight stability, defined as a maximum variation of ±3% between the highest and lowest recorded body weight during the 3 months prior to inclusion. - Informed oral and written consent Who Should NOT Join This Trial: - Anaemia - Alanine aminotransferase (ALAT) \> 2 times normal value - History of hepatobiliary and/or gastrointestinal disorder - Kidney disease (serum creatinine above normal range and/or urine albumin-creatinine ratio 30mg/g confirmed with two measurements) - Any ongoing medication that investigator evaluates would interfere with study participation - Any physical or psychological condition that investigators evaluate would interfere with study participation including any acute or chronic illnesses. - Regular tobacco smoking and/or use of other nicotine products - Glycated haemoglobin HbA1c \> 48 and/or type 1 or type 2 diabetes medical treatment - Women of childbearing potential who are not using effective contraception - Pregnancy or breastfeeding Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Age between 18 and 65 years old * Body mass index (BMI) above ≥ 25 kg/m2 * Ongoing semaglutide treatment with a stable dose of ≥ 1 mg once weekly for a minimum of 3 months prior to inclusion * Weight stability, defined as a maximum variation of ±3% between the highest and lowest recorded body weight during the 3 months prior to inclusion. * Informed oral and written consent Exclusion Criteria: * Anaemia * Alanine aminotransferase (ALAT) \> 2 times normal value * History of hepatobiliary and/or gastrointestinal disorder * Kidney disease (serum creatinine above normal range and/or urine albumin-creatinine ratio 30mg/g confirmed with two measurements) * Any ongoing medication that investigator evaluates would interfere with study participation * Any physical or psychological condition that investigators evaluate would interfere with study participation including any acute or chronic illnesses. * Regular tobacco smoking and/or use of other nicotine products * Glycated haemoglobin HbA1c \> 48 and/or type 1 or type 2 diabetes medical treatment * Women of childbearing potential who are not using effective contraception * Pregnancy or breastfeeding

Treatments Being Tested

BIOLOGICAL

Liver-Expressed Antimicrobial Peptide 2 (LEAP2)

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

OTHER

Placebo (saline)

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

Locations (1)

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, Denmark