GIP/GLP-1 Co-Activity in Subjects With Overweight and Type 2 Diabetes: Lowering of Food Intake

Study Overview
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Brief Summary
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The primary aim of the study is to evaluate how GIP receptor activation influence food intake and mechanisms regulating food intake in obese individuals with type 2 diabetes that are in steady treatment with metformin and a GLP-1 receptor agonist.

Detailed Description
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The study is designed as a double blinded cross-over study with two study days: One day of GIP infusion (for 5 hours) and one day with placebo (saline) infusion (for 5 hours). The primary endpoint is difference in food intake between the two study days. Food intake is examined as amount of food eaten during an ad libitum meal.

Official Title
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GIP/GLP-1 Co-Activity in Subjects With Overweight and Type 2 Diabetes: Lowering of Food Intake

Conditions
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Type 2 Diabetes Mellitus, Overweight and Obesity

Intervention / Treatment
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* Biological: GIP1-42 infusion
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Caucasian men Age between 18 and 70 years Body mass index (BMI) between 25 and 40 kg/m2 Type 2 diabetes (diagnosed according to the criteria of the World Health Organization) with HbA1c <69 mM (<8.5 %) In stable treatment for ≥3 months with metformin ≥1 g and a GLP-1 receptor agonist. Informed consent Exclusion criteria Anaemia (haemoglobin outside normal range) Any current or prior gastrointestinal disease that may interfere with the endpoint variables Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) > 2 times normal values) or history of hepatobiliary disorder. Nephropathy (serum creatinine above normal range and/or albuminuria). Anorexia, bulimia or binge eating disorder Allergy or intolerance to ingredients included in the standardised meals Tobacco smoking Treatment with other glucose lowering drugs than GLP-1 receptor agonists and metformin. Any regular drug treatment (besides metformin and GLP-1 receptor agonists) that cannot be discontinued for a minimum of 12 hours Any physical or psychological condition that the investigator feels would interfere with trial participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GIP infusion<br>5 hours of continuously GIP1-42 infusion | Biological: GIP1-42 infusion<br>* 5-hour GIP1-42 infusion (time point 0-300 minutes)<br>|
| Placebo Comparator: Saline<br>5 hours of continuously saline infusion | Other: Saline<br>* 5-hour infusion of saline (placebo) (time point 0-300 minutes)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| food intake | food intake (kJ) eaten from an ad libitum meal of pasta bolognese | time point 300-330 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appetite | Appetite rated on visual analogue scales (0-10 mm) | time point -30, 0, 30, 60, 90, 120, 150, 180, 210, 240, 270 minutes | 
| satiety | Satiety rated on visual analogue scales (0-10 mm) | time point -30, 0, 30, 60, 90, 120, 150, 180, 210, 240, 270 minutes | 
| prospective food consumption | prospective food consumption rated on visual analogue scales (0-10 mm) | time point -30, 0, 30, 60, 90, 120, 150, 180, 210, 240, 270 minutes | 
| fullness | fullness rated on visual analogue scales (0-10 mm) | time point -30, 0, 30, 60, 90, 120, 150, 180, 210, 240, 270 minutes | 
| Thirst | Thirst rated on visual analogue scales (0-10 mm) | time point -30, 0, 30, 60, 90, 120, 150, 180, 210, 240, 270 minutes | 
| Nausea | Nausea rated on visual analogue scales (0-10 mm) | time point -30, 0, 30, 60, 90, 120, 150, 180, 210, 240, 270 minutes | 
| Energy expenditure | resting energy expenditure measured by indirect calorimetry (kcal/day) | measured at baseline and at time point 250 minutes | 
| gastric emptying | acetaminophen test | ingested at time point -15, 0, 60, 75, 90, 105, 120, 150, 180, 210 and 270 minutes | 
| gallbladder emptying | gallbladder emptying evaluated by ultrasound | at time point -15, 0, 30, 60, 90, 120, 150, 180, 240 minutes | 
| glucagon responses | blood samples | at time point -15, 0, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 and 270 minutes | 
| Insulin responses | blood samples | at time point -15, 0, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 and 270 minutes | 
| C-peptide responses | blood samples | at time point -15, 0, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 and 270 minutes | 
| gut hormone responses | Blood samples | at time point -15, 0, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 and 270 minutes | 
| bone turnover markers | Blood samples | at time point -15, 0, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 and 270 minutes |