Glucose-dependent insulinotropic polypeptide (GIP) is released by the intestines in response to food intake and increases insulin secretion. Although short-term (< 3 hours) stimulation with GIP decreases bone resorption in humans, the effect may vanish following continuous administration within 24 hours, at least in patients with type 1 diabetes. Whether the anti-resorptive effect of GIP can be maintained if the hormone is non-continuously administrated is unclear. As the first GIP receptor (GIPR) agonist, tirzepatide was recently approved for the treatment of obesity and type 2 diabetes in the USA and type 2 diabetes alone in the EU, there is a need to establish knowledge about the long-term effects of GIP on bone health, including if different exposure times to GIP have different skeletal effects.

This project will investigate whether GIP maintains its anti-resorptive potential if given as intermittent compared to continuous infusion in healthy men and women aged 18-40 years. Administration cycles involve intermittent (8 hours daily) and continuous (24 hours daily) injection of GIP for three days each. The effect of GIP will be measured by bone markers in blood samples, as well as in vitro activity and genetic alterations of bone cells (osteoclasts and osteoblasts) using bone marrow aspirates and bone marrow biopsies. Each participant will receive both administration cycles using a crossover design with a 14-28 days washout period between administrations of GIP.

Inclusion Criteria:

• healthy volunteers

Exclusion Criteria:

• pre-diabetes or diabetes (HbA1c >42mmol/mol)
• BMI >28
• fractures with < 6months
• comorbidities/treatments that may influence bone metabolism or procedures - -- pregnancy
• inability to provide informed concent

individual participant data will not be shared following GDPR and local data mangament regulation. However data(anonymous) and results will be published once the study is completed.