Separate and Combined Extrapancreatic Effects of the Incretin Hormones

Not Applicable

Completed

• Conditions: Pancreatectomy; Hyperglycemia

• Registration Number: NCT05177653
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-16
• Study First Submitted QC: 2021-12-14
• Study First Posted: 2022-01-04
• Study Start: 2022-04-07
• Status Verified: 2023-03
• Primary Completion: 2023-03-03
• Study Completion: 2023-03-03
• Last Update Submitted: 2023-03-28
• Last Update Posted: 2023-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

• Total pancreatectomy
• Caucasians
• Blood haemoglobin >7 mmol/l for males and >6.5 mmol/l for females

Exclusion Criteria

• Pancreatectomy within the last 3 months
• Ongoing chemotherapy or chemotherapy within the last 3 months
• Treatment with GLP-1R agonists within the last 3 months
• Renal impairment (estimated by eGFR <60 ml/min/1.73 m2) and/or albuminuria
• Calcium related disease, hypo-/hyperthyroidism
• Known significant liver disease, ALT or AST >3 times normal value or INR outside normal range
• Severe arteriosclerotic heart disease or heart failure (NYHA group III or IV)
• Pregnancy and/or breastfeeding
• Use of more than 14 units of alcohol per week or abuse of narcotics
• Any condition that the investigator feels would interfere with trial participation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days	Up to two months	mmol/l
Changes in CTX between interventions assessed through frequently blood sampling during the experimental days	Up to two months	ng/ml
Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days	Up to two months	pmol/l
Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days.	Up to two months	mmol/l lipoproteins, neutral and complex lipids.
Changes in adiponectin in plasma between interventions, assessed through frequently blood sampling during the experimental days.	Up to two months	μg/mL
Changes in plasma lipoproteins between interventions assessed through frequently blood sampling during the experimental days.	Up to two months	mg/dl
Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days	Up to two months	pmol/l
Changes in plasma P1NP between interventions assessed through frequently blood sampling during the experimental days	Up to two months	ng/ml
Changes in brown adipose tissue activity between interventions, assessed by thermographic camera	Up to two months

Trial Locations

Locations (1)

Center for Clinical Metabolic Research; 🇩🇰 Hellerup, Denmark