The present study investigates the postprandial role of endogenous glucose-dependent insulinotropic polypeptide (GIP) on cardiovascular haemodynamics, hormone responses, and hypotensive symptoms during a tilt test.

The study is an exploratory, randomised, placebo-controlled, double-blinded crossover study comprising four experimental days. Each experimental day consists of a mixed meal test or drinking water, a double-blinded continuous infusion of GIP(3-30)NH2 or placebo or GIP(1-42) or placebo, and three tilt tests. Sixteen healthy men and women will be included in the study.

Inclusion Criteria:

1. Age 18-40 years
2. BMI between 18.5 and 29.9 kg/m2 (both included)
3. Informed consent

Exclusion Criteria:

1. Allergy or intolerance to ingredients included in the mixed meal
2. History of Orthostatic Hypotension (OH) or Postural Orthostatic Tachycardia Syndrome (POTS) or other autonomic dysfunction at the discretion of the investigators
3. Anaemia (haemoglobin below normal range <7.3 mmol/L for women and <8.3 mmol/L for men)
4. Kidney disease (estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2) at screening
5. Known liver disease and/or elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal at screening
6. Treatment with antihypertensives
7. Treatment with GLP-1RA (Glucagon-like Peptide-1 Receptor Agonist)
8. Treatment with SNRI (Serotonin and Noradrenalin Reuptake Inhibitor) or treatment within two weeks before the first experimental day
9. Any ongoing medication that the investigator evaluates would interfere with trial participation
10. Any physical or psychological condition that the investigator evaluates would interfere with trial participation, including any acute or chronic illnesses
11. Any concomitant disease or treatment that, at the discretion of the investigators, might jeopardize the participant's safety during the trial
12. Alcohol/drug abuse as per discretion of the investigators
13. Pregnancy or breastfeeding
14. Participation in any other clinical trial during the study period
15. Mental incapacity or language barriers that preclude adequate understanding or cooperation or unwillingness to comply with trial requirements or pr discretion of the investigator