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Separate and Combined Extrapancreatic Effects of the Incretin Hormones

Not Applicable
Completed
Conditions
Pancreatectomy; Hyperglycemia
Interventions
Other: Intravenous infusion
Registration Number
NCT05177653
Lead Sponsor
University Hospital, Gentofte, Copenhagen
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
13
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
GLP-1RAIntravenous infusion-
GIPRA + GLP-1RAIntravenous infusion-
SalineIntravenous infusion-
GIPRAIntravenous infusion-
Primary Outcome Measures
NameTimeMethod
Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental daysUp to two months

mmol/l

Changes in CTX between interventions assessed through frequently blood sampling during the experimental daysUp to two months

ng/ml

Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental daysUp to two months

pmol/l

Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days.Up to two months

mmol/l lipoproteins, neutral and complex lipids.

Changes in adiponectin in plasma between interventions, assessed through frequently blood sampling during the experimental days.Up to two months

μg/mL

Changes in plasma lipoproteins between interventions assessed through frequently blood sampling during the experimental days.Up to two months

mg/dl

Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental daysUp to two months

pmol/l

Changes in plasma P1NP between interventions assessed through frequently blood sampling during the experimental daysUp to two months

ng/ml

Changes in brown adipose tissue activity between interventions, assessed by thermographic cameraUp to two months
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Center for Clinical Metabolic Research

🇩🇰

Hellerup, Denmark

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