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

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Pancreatectomy; Hyperglycemia

Treatments: Other: Intravenous Infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT06895408

101292 (H-21035117)

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 30 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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12 participants in 4 patient groups, including a placebo group

GIP

Experimental group

Description:

Intravenous infusion of glucose-dependent insulinotropic polypeptide

Treatment:

Other: Intravenous Infusion

Other: Intravenous Infusion

Other: Intravenous Infusion

Other: Intravenous Infusion

GLP-1

Experimental group

Description:

Intravenous infusion of glucagon-like peptide 1

Treatment:

Other: Intravenous Infusion

Other: Intravenous Infusion

Other: Intravenous Infusion

Other: Intravenous Infusion

GIP + GLP-1

Experimental group

Description:

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

Treatment:

Other: Intravenous Infusion

Other: Intravenous Infusion

Other: Intravenous Infusion

Other: Intravenous Infusion

Saline

Placebo Comparator group

Description:

Intravenous infusion of saline

Treatment:

Other: Intravenous Infusion

Other: Intravenous Infusion

Other: Intravenous Infusion

Other: Intravenous Infusion