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

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Pancreatectomy; Hyperglycemia

Treatments: Other: Intravenous infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT05177653

H-21035117

Details and patient eligibility

About

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.

Enrollment: 13 patients

Sex: All

Ages: 30 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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13 participants in 4 patient groups, including a placebo group

GIPRA

Experimental group

Treatment:

Other: Intravenous infusion

Other: Intravenous infusion

Other: Intravenous infusion

Other: Intravenous infusion

GLP-1RA

Experimental group

Treatment:

Other: Intravenous infusion

Other: Intravenous infusion

Other: Intravenous infusion

Other: Intravenous infusion

GIPRA + GLP-1RA

Experimental group

Treatment:

Other: Intravenous infusion

Other: Intravenous infusion

Other: Intravenous infusion

Other: Intravenous infusion

Saline

Placebo Comparator group

Treatment:

Other: Intravenous infusion

Other: Intravenous infusion

Other: Intravenous infusion

Other: Intravenous infusion