GA 6: The Blood Glucose-lowering Effect of Glucose-dependent Insulinotropic Polypeptide

Study Overview
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Brief Summary
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This study will investigate if the effect of DPP-4 inhibitors is mediated in part by Glucose-dependent insulinotropic polypeptide.

Detailed Description
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A randomized, placebo controlled study. Using a GIP receptor antagonist, we will investigate the glucose lowering effect of GIP during treatment with DPP-4 inhibitors.

Official Title
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The Blood Glucose-lowering Effect of Glucose-dependent Insulinotropic Polypeptide

Conditions
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Type2 Diabetes

Intervention / Treatment
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* Other: Placebo
* Other: GIP receptor antagonist
* Drug: DPP-4 inhibitor
* Other: Placebo tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 2 diabetes, treatment: lifestyle changes or metformin HbA1c < 75 mmol/mol Exclusion Criteria: diagnosed liver disease eGFR < 60 ml/min/1,73m2 NYHA III or IV anemia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, placebo-controlled, cross-over.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo tablet for placebo treatment period. Following treatment: 2 separate interventions/study days (placebo infusion and GIP receptor antagonist) | Other: Placebo<br>* Saline infusion<br>Other: GIP receptor antagonist<br>* Used for infusion on study days<br>Other: Placebo tablet<br>* Oral administration of placebo tablet in placebo treatment period<br>|
| Active Comparator: DPP-4 inhibitor<br>DPP-4 inhibitor treatment for active treatment period. Following treatment: 2 separate interventions/study days (placebo infusion and GIP receptor antagonist) | Other: Placebo<br>* Saline infusion<br>Other: GIP receptor antagonist<br>* Used for infusion on study days<br>Drug: DPP-4 inhibitor<br>* Oral administration of DPP-4 inhibitor in active treatment period<br>* Other names: Sitagliptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-peptide | Concentrations of C-peptide during GIP receptor antagonism compared to placebo | 5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glucose | Concentrations of plasma glucose during GIP receptor antagonism compared to placebo | 5 hours | 
| Insulin | Concentrations of insulin during GIP receptor antagonism compared to placebo | 5 hours | 
| Total and intact GIP | Concentrations of total and intact GIP during GIP receptor antagonism compared to placebo | 5 hours | 
| Total and intact GLP-1 | Concentrations of total and intact GLP-1 during GIP receptor antagonism compared to placebo | 5 hours | 
| Glucagon | Concentrations of glucagon during GIP receptor antagonism compared to placebo | 5 hours | 
| CTX | Concentrations of CTX during GIP receptor antagonism compared to placebo | 5 hours | 
| Lipids | Concentrations of lipids during GIP receptor antagonism compared to placebo | 5 hours |