Separate and Combined Extrapancreatic Effects of the Incretin Hormones (GA-19)

Separate and Combined Extrapancreatic Effects of Glucose-dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1

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.

Study Overview

• Status: Completed
• Conditions: Pancreatectomy; Hyperglycemia
• Intervention / Treatment: Other: Intravenous infusion; Other: Intravenous infusion; Other: Intravenous infusion; Other: Intravenous infusion

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Center for Clinical Metabolic Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline	Other: Intravenous infusion; GIP receptor antagonist (GIP(3-30)NH2); Other: Intravenous infusion; GLP-1 receptor antagonist (exendin(9-39)NH2); Other: Intravenous infusion; GIP(3-30)NH2 and exendin(9-39)NH2; Other: Intravenous infusion; Saline
Experimental: GIPRA	Other: Intravenous infusion; GIP receptor antagonist (GIP(3-30)NH2); Other: Intravenous infusion; GLP-1 receptor antagonist (exendin(9-39)NH2); Other: Intravenous infusion; GIP(3-30)NH2 and exendin(9-39)NH2; Other: Intravenous infusion; Saline
Experimental: GLP-1RA	Other: Intravenous infusion; GIP receptor antagonist (GIP(3-30)NH2); Other: Intravenous infusion; GLP-1 receptor antagonist (exendin(9-39)NH2); Other: Intravenous infusion; GIP(3-30)NH2 and exendin(9-39)NH2; Other: Intravenous infusion; Saline
Experimental: GIPRA + GLP-1RA	Other: Intravenous infusion; GIP receptor antagonist (GIP(3-30)NH2); Other: Intravenous infusion; GLP-1 receptor antagonist (exendin(9-39)NH2); Other: Intravenous infusion; GIP(3-30)NH2 and exendin(9-39)NH2; Other: Intravenous infusion; Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2022
• Primary Completion (Actual): March 3, 2023
• Study Completion (Actual): March 3, 2023

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia
• Other Study ID Numbers: H-21035117

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No