This research project aims to investigate the role of endogenous GIP during fasting. With the infusion of a GIP receptor antagonist (GIP[3-30]NH2), is it possible to selectively remove the effect of endogenous GIP, and thus describe its effects by comparing it with what happens during a saline infusion.

This research project investigates the effects endogenous GIP has in the body of healthy, overweight people. Two trial days will be held. The participant will receive intravenous infusion of either GIP[3-30]NH2 (800 pmol/kg/min) or placebo (saline) in a randomized order. After 20 minutes, GIP[3-30]NH2 is expected to have maximum effect. On time of 180 minutes, an ad libitum meal is served, which is consumed during continued infusion. When the participant is comfortably full, the infusion is turned off and the trial day ends. During the day, the participant assesses and notes on standardized VAS schedules current appetite, satiety, nausea, fatigue, malaise and thirst. Blood pressure and heart rate are measured every 30 minutes throughout the trial day and blood samples are taken. In total, there will be drawn ten blood samples between intervals of 15 to 30 min. Three times along the way, the activity in the brown adipose tissue is measured with a thermal camera (temperature measurements over the skin on the chest) and the resting metabolic rate is determined with indirect calorimetry (inhaled and exhaled air is captured by breathing under a large plastic bell).

Inclusion Criteria:

• 18-70 years
• BMI > 30 kg/m2
• Body fat percentage > 25 % for men og > 35 % for women

Exclusion Criteria:

• Type 1 diabetes and/or type 2 diabetes diagnosis
• Other chronic condition
• Treatment with medications or supplements that cannot be paused for 12 hours
• > 14 units of alcohol weekly or drug abuse
• Circulating liver enzymes (alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT)) ≥ 2 × normal value
• Renal impairment (eGFR < 90 or creatinine level above the reference range)
• Uncontrolled high resting blood pressure (above 140/90 mmHg)
• Low blood percentage (hemoglobin < reference range (different for women and men))
• Special diet or planned weight change within the trial period
• Any disease/condition that investigators believe will interfere with study participation

The results of this project or sub-elements of the project will be compiled into one or more manuscripts for publication in one or more international scientific high impact journals. All results, both inconclusive, negative and positive trial results, will be published as soon as possible. All trial participants will be informed in writing of the results after the end of the trial.

December 31st. 2025

The infusion is mixed by an external coordinator. Neither the investigator or the participants knows whether is the GIP[3-30]NH2 infusion or saline infusion that is being given. Which infusion that is given on each trial day is randomized for each participant.