Separate and Combined Extrapancreatic Effects of Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide 1 (GLP-1)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Plasma glucose
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 30 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
GIP
Intravenous infusion of glucose-dependent insulinotropic polypeptide
Intervention: Intravenous Infusion (Other)
GLP-1
Intravenous infusion of glucagon-like peptide 1
Intervention: Intravenous Infusion (Other)
GIP + GLP-1
Intravenous infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1
Intervention: Intravenous Infusion (Other)
Saline
Intravenous infusion of saline
Intervention: Intravenous Infusion (Other)
Outcomes
Primary Outcomes
Plasma glucose
Time Frame: Up to two months
Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days
Plasma glucagon
Time Frame: Up to two months
Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days
Plasma Insulin/C-peptide
Time Frame: Up to two months
Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days
Plasma triglycerides
Time Frame: Up to two months
Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days
Plasma CTX
Time Frame: Up to two months
Changes in CTX between interventions assessed through frequently blood sampling during the experimental days
Plasma PINP
Time Frame: Up to two months
Changes in plasma PINP between interventions assessed through frequently blood sampling during the experimental days
Secondary Outcomes
No secondary outcomes reported
Investigators
Asger Lund, MD
Clinical Associate Professor
University Hospital, Gentofte, Copenhagen