Separate and Combined Extrapancreatic Effects of GIP and GLP-1

NCT06895408 | Completed

• 1 other identifier: 101292 (H-21035117)
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatectomy; Hyperglycemia

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (4)

GIP

EXPERIMENTAL

Intravenous infusion of glucose-dependent insulinotropic polypeptide

Other: Intravenous Infusion

GLP-1

EXPERIMENTAL

Intravenous infusion of glucagon-like peptide 1

Other: Intravenous Infusion

GIP + GLP-1

EXPERIMENTAL

Intravenous infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1

Other: Intravenous Infusion

Saline

PLACEBO COMPARATOR

Intravenous infusion of saline

Other: Intravenous Infusion

Interventions

Intravenous Infusion OTHER

Glucose-dependent Insulinotropic Polypeptide

GIP

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Total pancreatectomy
• Caucasians between 30-75 years of age
• Blood haemoglobin \>7.0 mmol/l for males and \>6.5 mmol/l for females

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead

Study Sites (1)

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, 2900, Denmark

Location

MeSH Terms

Conditions

Hyperglycemia

Interventions

Infusions, Intravenous

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: March 26, 2025
• Study Start: February 19, 2025
• Primary Completion: July 14, 2025
• Study Completion: July 14, 2025
• Last Updated: September 9, 2025

Record last verified: 2025-09

Locations

DK (1)