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The two gut-derived hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) is 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 |
|---|---|---|---|
| GIPRA | Experimental |
| |
| GLP-1RA | Experimental |
| |
| GIPRA + GLP-1RA | Experimental |
| |
| Saline | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous infusion | Other | GIP receptor antagonist (GIP(3-30)NH2) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days | mmol/l | Up to two months |
| Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days | pmol/l | Up to two months |
| Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days | pmol/l | Up to two months |
| Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days. | mmol/l lipoproteins, neutral and complex lipids. | Up to two months |
| Changes in plasma lipoproteins between interventions assessed through frequently blood sampling during the experimental days. | mg/dl | Up to two months |
| Changes in brown adipose tissue activity between interventions, assessed by thermographic camera | Up to two months | |
| Changes in adiponectin in plasma between interventions, assessed through frequently blood sampling during the experimental days. | μg/mL | 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 | Hellerup | 2900 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41069310 | Derived | Krogh LSL, Helsted MM, Englund A, Bergmann NC, Skov-Jeppesen K, Nielsen CK, Hansen CP, Rosenkilde MM, Hartmann B, Holst JJ, Knop FK, Lund AB, Gasbjerg LS. Acute effects of GIP and GLP-1 receptor antagonism in totally pancreatectomized individuals: A randomized double-blind, placebo-controlled crossover study. Diabetes Obes Metab. 2026 Jan;28(1):275-286. doi: 10.1111/dom.70186. Epub 2025 Oct 10. |
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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 |
GLP-1 receptor antagonist (exendin(9-39)NH2) |
|
| Intravenous infusion | Other | GIP(3-30)NH2 and exendin(9-39)NH2 |
|
| Intravenous infusion | Other | Saline |
|
| Changes in CTX between interventions assessed through frequently blood sampling during the experimental days |
ng/ml |
| Up to two months |
| Changes in plasma P1NP between interventions assessed through frequently blood sampling during the experimental days | ng/ml | Up to two months |
| D007263 |
| Infusions, Parenteral |