LEAP2's effect on appetite control in people taking semaglutide

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

This trial tries giving LEAP2 to adults with overweight or obesity who are on semaglutide to see if blocking the ghrelin receptor lowers hunger, reduces food intake, and changes glucose and hormone responses.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University Hospital, Gentofte, Copenhagen (Academic / other)
• Locations: 1 site (Hellerup)
• Trial ID: NCT07171723 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled crossover trial enrolls 24 adults with overweight or obesity who have been on a stable weekly semaglutide dose (≥1 mg) for at least three months. Each participant completes two experimental visits and receives a 6-hour intravenous infusion of either LEAP2 or saline on separate days while investigators measure ad libitum food intake, appetite sensations, glucose metabolism, and hormone levels. The design uses within-subject comparisons to isolate the effect of transient ghrelin receptor blockade during pharmacological GLP-1 receptor activation. Results will clarify whether ghrelin signaling remains a meaningful driver of hunger and metabolic responses when appetite is suppressed by semaglutide.

Who should consider this trial

Good fit: Adults aged 18–65 with BMI ≥25 kg/m2 who are weight-stable and have been on a stable semaglutide dose of at least 1 mg weekly for a minimum of three months are the intended participants.

Not a fit: People not taking semaglutide, those outside the age or BMI ranges, individuals with unstable weight or significant liver, kidney, gastrointestinal disease, active smoking, or other exclusions are unlikely to benefit from joining this mechanistic trial.

Why it matters

Potential benefit: If successful, the findings could show whether adding ghrelin-receptor blockade to GLP-1 therapy might further reduce hunger or improve metabolic control for people with obesity.

How similar studies have performed: Previous small human studies reported that LEAP2 infusion can reduce ad libitum food intake and postprandial glucose in lean and obese participants, but combining LEAP2 with GLP-1 receptor agonist treatment has not been tested.

Eligibility criteria

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

Where this trial is running

Hellerup

• Center for Clinical Metabolic Research, Gentofte Hospital — Hellerup, Denmark (Recruiting)

Study contacts

• Study coordinator: Christian Legart, MD

Conditions Obesity &Amp; Overweight