The Effect of GLP-1 on Postprandial Glucagon Secretion Independent of The Gastric Emptying Rate

Study Overview
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Brief Summary
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Aim: To investigate the glucagonostatic effect of glucagon-like peptide-1 (GLP-1) independent of the gastric emptying rate.

Detailed Description
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Aim: To investigate the glucagonostatic effects of glucagon-like peptide-1 (GLP-1) during prolonged and intermittent stimulation of the GLP-1 receptor independent of the gastric emptying rate. Glucagon concentrations will be measured following a liquid meal administered in duodenum at baseline and after exenatide, and liraglutide treatment.

Official Title
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The Effect of GLP-1 on Postprandial Glucagon Secretion During Prolonged and Intermittent Stimulation of the GLP-1 Receptor Independent of The Gastric Emptying Rate. A Randomized, Open-label Study in People With Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Exenatide
* Procedure: Liquid meal test
* Other: No drug (Baseline day)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 Diabetes >18 years No residual beta-cell function (stimulated C-peptide < 60 pmol) Exclusion Criteria: Pancreatitis gastroparesis history of alcohol and/or drug abuse pregnancy and lactation other medical or psychological condition that made the patient unsuitable for study participation according to the investigators´ assessment contraindications to gastroscopy cancer (unless in complete remission > five years)

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide + Liquid meal test<br>Liraglutide 1.2 mg once daily for 14 days (0.6 mg/day for one week, escalated to 1.2 mg/day after one week) | Drug: Liraglutide<br> <br> Procedure: Liquid meal test<br> <br> |
| Experimental: Exenatide + Liquid meal test<br>Exenatide 10 mcg twice daily for 14 days (5 mcg twice daily for one week, escalated to 10 mcg twice daily after one week) | Drug: Exenatide<br> <br> Procedure: Liquid meal test<br> <br> |
| Other: Baseline + Liquid meal test<br>Baseline day with no additional medication | Procedure: Liquid meal test<br> <br> Other: No drug (Baseline day)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon concentration (postprandial) | glucagon area under the curve (AUC) (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glucose concentrations | glucose AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| glucagon-like peptide-1 (GLP-1) | GLP-1 AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| glucagon-like peptide-2 (GLP-2) | GLP-2 AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| glucose-dependent insulinotropic polypeptide (GIP) | GIP AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| Cholecystokinin (CCK) | CCKAUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| Peptide YY (PYY) | PYY AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| Ghrelin | Ghrelin AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| Gastrin | Gastrin AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| Oxyntomodulin | Oxyntomodulin AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| Free fatty acids (FFA) | FFA AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 
| triacylglycerol (TAG) | TAG AUC (0-240 minutes) and baseline to peak increments will be calculated | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucagon, Glukagon-like peptide-1 (GLP-1), GLP-1 receptor agonist (GLP-1RA), Incretins