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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Overweight and Obesity
• Intervention / Treatment: Biological: GIP1-42 infusion; Other: Saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, DK-2900
    • Center for diabetes research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: Zealand Pharma

Publications and helpful links

General Publications

• Bergmann NC, Gasbjerg LS, Heimburger SM, Krogh LSL, Dela F, Hartmann B, Holst JJ, Jessen L, Christensen MB, Vilsboll T, Lund A, Knop FK. No Acute Effects of Exogenous Glucose-Dependent Insulinotropic Polypeptide on Energy Intake, Appetite, or Energy Expenditure When Added to Treatment With a Long-Acting Glucagon-Like Peptide 1 Receptor Agonist in Men With Type 2 Diabetes. Diabetes Care. 2020 Mar;43(3):588-596. doi: 10.2337/dc19-0578. Epub 2020 Jan 16.

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2017
• Primary Completion (Actual): October 24, 2018
• Study Completion (Actual): October 24, 2018

Study Registration Dates

• First Submitted: October 24, 2017
• First Submitted That Met QC Criteria: May 3, 2018
• First Posted (Actual): May 16, 2018

Study Record Updates

• Last Update Posted (Actual): December 5, 2018
• Last Update Submitted That Met QC Criteria: December 4, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight
• Other Study ID Numbers: H-16031728

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No