GIP/GLP-1 Co-Activity in Subjects With Obesity: Lowering of Food Intake

Not Applicable

Completed

• Conditions: Type 2 Diabetes; Obesity; Adiposity
• Interventions: Other: IIGI+GIP; Other: IIGI+GLP-1; Other: IIGI+NaCl (placebo); Other: OGTT; Other: IIGI+GIP+GLP-1

• Registration Number: NCT02598791
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

We aim to delineate the effects of separate and combined infusion of GIP and GLP-1 on food intake, appetite, bone health and fat metabolism in overweight/obese subjects.

Detailed Description

The gut-derived incretin glucagon-like peptide-1 (GLP-1) is a potent regulator of gastric emptying, appetite and food intake in humans whereas its sister incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), does not seem to have independent effects on these variables in humans. Interestingly, recent data from rodents have shown that concomitant activation of the GIP and the GLP-1 receptor may potentiate the satiety-promoting and body weight-reducing effects of GLP-1. Also, evidence suggests that GIP may be an important mediator of bone remodelling and lipid deposition. The effect of simultaneous activation of the GIP and GLP-1 receptors on appetite, food intake, fat metabolism and bone health has not been thoroughly examined in humans. The aim of this study is to delineate the effects of GIP/GLP-1 receptor co-activation on food intake, mechanisms regulating food intake, fat and bone metabolism in obese subjects.

Material and methods:

The investigators plan to include 18 obese/overweight men without diabetes. The primary endpoint of the study is food intake during continuous intravenous infusions of saline (placebo), GIP, GLP-1 and GIP+GLP-1, respectively. Secondary endpoints includes resting energy expenditure (measured by indirect calorimetry), appetite, satiety and hunger assessments (measured by visual analogue scales), plasma insulin, C-peptide and glucagon secretion, plasma triglycerides, cholesterols, and free fatty acid responses and changes in plasma bone turnover markers.

Study Timeline

• Study Start: 2015-10-01
• Study First Submitted: 2015-10-31
• Study First Submitted QC: 2015-11-05
• Study First Posted: 2015-11-06
• Primary Completion: 2016-06-20
• Study Completion: 2016-06-20
• Status Verified: 2018-12
• Last Update Submitted: 2018-12-04
• Last Update Posted: 2018-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

• Caucasian men
• Age between 25 and 70 years
• Body mass index (BMI) between 25 and 40 kg/m2

Exclusion Criteria

• Diabetes or prediabetes (defined as glycated haemoglobin (HbA1c) ≥ 43 mmol/mol)
• Anaemia (defined as haemoglobin < 8.3 mmol/l)
• Any gastrointestinal disease that may interfere with the endpoint variables
• Anorexia, bulimia or binge eating disorder
• Allergy or intolerance to ingredients included in the standardised meals
• Tobacco smoking
• Any regular drug treatment that cannot be discontinued for minimum 18 hours
• Any physical or psychological condition that the investigator feels would interfere with trial participation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
50 g OGTT	IIGI+NaCl (placebo)	50 g oral glucose tolerance test (OGTT)
50 g OGTT	OGTT	50 g oral glucose tolerance test (OGTT)
IIGI+GIP	IIGI+GIP	4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
IIGI+GIP	IIGI+NaCl (placebo)	4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
IIGI+GIP	IIGI+GLP-1	4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
IIGI+GLP-1	IIGI+GIP	4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
IIGI+GLP-1	IIGI+NaCl (placebo)	4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
IIGI+NaCl (placebo)	IIGI+GIP	4 hour i.v. NaCl (placebo) during isoglycemic conditions
IIGI+GIP+GLP-1	IIGI+GIP	4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
50 g OGTT	IIGI+GIP	50 g oral glucose tolerance test (OGTT)
IIGI+GLP-1	OGTT	4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
IIGI+NaCl (placebo)	IIGI+NaCl (placebo)	4 hour i.v. NaCl (placebo) during isoglycemic conditions
IIGI+GIP+GLP-1	IIGI+GLP-1	4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
IIGI+GIP+GLP-1	IIGI+NaCl (placebo)	4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
IIGI+GIP+GLP-1	IIGI+GIP+GLP-1	4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
IIGI+GIP	OGTT	4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
IIGI+NaCl (placebo)	IIGI+GLP-1	4 hour i.v. NaCl (placebo) during isoglycemic conditions
IIGI+GIP+GLP-1	OGTT	4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
50 g OGTT	IIGI+GLP-1	50 g oral glucose tolerance test (OGTT)
IIGI+GIP	IIGI+GIP+GLP-1	4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
IIGI+GLP-1	IIGI+GLP-1	4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
IIGI+GLP-1	IIGI+GIP+GLP-1	4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
IIGI+NaCl (placebo)	OGTT	4 hour i.v. NaCl (placebo) during isoglycemic conditions
IIGI+NaCl (placebo)	IIGI+GIP+GLP-1	4 hour i.v. NaCl (placebo) during isoglycemic conditions
50 g OGTT	IIGI+GIP+GLP-1	50 g oral glucose tolerance test (OGTT)

Primary Outcome Measures

Name	Time	Method
food intake	250-280 min	How much does the participant eat of from the ad libitum meal, measured in gram

Secondary Outcome Measures

Name	Time	Method
hunger	measured at time 0, 30, 60, 90, 120, 180, 210, 240 min	feeling of hunger measured on a visual analogue scale
Fullness	measured at time 0, 30, 60, 90, 120, 180, 210, 240 min	feeling of fullness measured on a visual analogue scale
satiety	measured at time 0, 30, 60, 90, 120, 180, 210, 240 min	feeling of satiety measured on a visual analogue scale
Prospective food consumption	measured at time 0, 30, 60, 90, 120, 180, 210, 240 min	Prospective food consumption measured on a visual analogue scale
resting energy expenditure (REE)	-15 to 0 min. and 210 to 225 min.	changes in REE measured by a ventilated hood 15 minutes at baseline and 15 minutes at time point 210 min.
Insulin	-30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min	changes in insulin measured in serum
C-peptide level	-30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min	changes in C-peptide level measured in serum
Cholesterol and FFA	-30, 0, 30, 60, 90, 120, 180, 240 min	changes in cholesterol (TAG, Total cholesterol and free fatty acid measured in plasma)
C-terminal cross-linked telopeptide of bone collagen (CTX)	-30, 0, 30, 60, 90, 120, 180, 240 min	changes in level of CTX measured in plasma
procollagen type 1 N-terminal propeptide (P1NP)	-30, 0, 30, 60, 90, 120, 180, 240 min	changes in level of P1NP measured in plasma
glucagon levels	-30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min	changes in glucagon levels measured in plasma

Trial Locations

Locations (1)

Center for Diabetesresearch, Gentofte hospital; 🇩🇰 Hellerup, Denmark