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The two gut-derived hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from intestinal cells in relation to a meal and increase insulin secretion from the pancreas. The hormones also exert effects outside the pancreas, but especially for GIP, these are poorly investigated. Because of this, only GLP-1 based drugs (GLP-1 receptor agonists) are on the market for the treatment of type 2 diabetes and obesity. Nonetheless, a new drug is in clinical development: a combined GIP-GLP-1-receptor agonist (tirzepatide), which has shown better results than GLP-1 alone. The mechanism behind these impressive effects are unknown and in this study, the investigators will look into the exptrapancreatic effects of GIP and GLP-1, separate and combined and thus elucidate the mechanisms of action of this new drug class.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GIP | Experimental | Intravenous infusion of glucose-dependent insulinotropic polypeptide |
|
| GLP-1 | Experimental | Intravenous infusion of glucagon-like peptide 1 |
|
| GIP + GLP-1 | Experimental | Intravenous infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 |
|
| Saline | Placebo Comparator | Intravenous infusion of saline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous Infusion | Other | Glucose-dependent Insulinotropic Polypeptide |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma glucose | Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days | Up to two months |
| Plasma glucagon | Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days | Up to two months |
| Plasma Insulin/C-peptide | Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days | Up to two months |
| Plasma triglycerides | Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days | Up to two months |
| Plasma CTX | Changes in CTX between interventions assessed through frequently blood sampling during the experimental days | Up to two months |
| Plasma PINP | Changes in plasma PINP between interventions assessed through frequently blood sampling during the experimental days | Up to two months |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Clinical Metabolic Research, Gentofte Hospital | Hellerup | 2900 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42225304 | Derived | Krogh LSL, Hansen MB, Bergmann NC, Hansen CP, Hartmann B, Holst JJ, Knop FK, Lund AB, Gasbjerg LS. Acute GIP and GLP-1 Administration Exerts Differential Metabolic Effects in Totally Pancreatectomised Individuals. Diabetes Obes Metab. 2026 Jun 1. doi: 10.1111/dom.70940. Online ahead of print. |
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| ID | Term |
|---|---|
| D006943 | Hyperglycemia |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D007262 | Infusions, Intravenous |
| ID | Term |
|---|---|
| D061605 | Administration, Intravenous |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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| Intravenous Infusion |
| Other |
Glucagon-Like Peptide 1 |
|
| Intravenous Infusion | Other | Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide 1 |
|
| Intravenous Infusion | Other | Saline |
|
| D007263 |
| Infusions, Parenteral |