Separate and Combined Extrapancreatic Effects of GIP and GLP-1 (GA-19b)

Separate and Combined Extrapancreatic Effects of Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide 1 (GLP-1)

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.

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): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Total pancreatectomy
• Caucasians between 30-75 years of age
• Blood haemoglobin >7.0 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-1 receptor agonists within the last 3 months
• Renal impairment (estimated by estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2) and/or albuminuria
• Calcium related disease, hypo-/hyperthyroidism
• Known significant liver disease, plasma alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 × normal value or INR (The international normalised ratio based on prothrombin time) outside the normal range
• Severe arteriosclerotic heart disease or heart failure (New York Heart Association (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
Experimental: GIP; Intravenous infusion of glucose-dependent insulinotropic polypeptide	Other: Intravenous Infusion; Glucose-dependent Insulinotropic Polypeptide; Other: Intravenous Infusion; Glucagon-Like Peptide 1; Other: Intravenous Infusion; Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide 1; Other: Intravenous Infusion; Saline
Experimental: GLP-1; Intravenous infusion of glucagon-like peptide 1	Other: Intravenous Infusion; Glucose-dependent Insulinotropic Polypeptide; Other: Intravenous Infusion; Glucagon-Like Peptide 1; Other: Intravenous Infusion; Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide 1; Other: Intravenous Infusion; Saline
Experimental: GIP + GLP-1; Intravenous infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1	Other: Intravenous Infusion; Glucose-dependent Insulinotropic Polypeptide; Other: Intravenous Infusion; Glucagon-Like Peptide 1; Other: Intravenous Infusion; Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide 1; Other: Intravenous Infusion; Saline
Placebo Comparator: Saline; Intravenous infusion of saline	Other: Intravenous Infusion; Glucose-dependent Insulinotropic Polypeptide; Other: Intravenous Infusion; Glucagon-Like Peptide 1; Other: Intravenous Infusion; Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide 1; Other: Intravenous Infusion; Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2025
• Primary Completion (Actual): July 14, 2025
• Study Completion (Actual): July 14, 2025

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: March 25, 2025
• First Posted (Actual): March 26, 2025

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Hyperglycemia; Therapeutics; Drug Administration Routes; Drug Therapy; Administration, Intravenous; Infusions, Parenteral; Infusions, Intravenous
• Other Study ID Numbers: 101292 (H-21035117)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No