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

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Adiposity; Obesity; Type 2 Diabetes

Treatments: Other: IIGI+GIP; Other: IIGI+GLP-1; Other: OGTT; Other: IIGI+NaCl (placebo); Other: IIGI+GIP+GLP-1

Study type: Interventional

Funder types: Other

Identifiers

NCT02598791

H-15008790 (GASOLIN)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: Male

Ages: 25 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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18 participants in 5 patient groups, including a placebo group

IIGI+GIP

Active Comparator group

Description:

4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions

Treatment:

Other: IIGI+GIP+GLP-1

Other: OGTT

Other: IIGI+GIP

Other: IIGI+NaCl (placebo)

Other: IIGI+GLP-1

IIGI+GLP-1

Active Comparator group

Description:

4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions

Treatment:

Other: IIGI+GIP+GLP-1

Other: OGTT

Other: IIGI+GIP

Other: IIGI+NaCl (placebo)

Other: IIGI+GLP-1

IIGI+NaCl (placebo)

Placebo Comparator group

Description:

4 hour i.v. NaCl (placebo) during isoglycemic conditions

Treatment:

Other: IIGI+GIP+GLP-1

Other: OGTT

Other: IIGI+GIP

Other: IIGI+NaCl (placebo)

Other: IIGI+GLP-1

IIGI+GIP+GLP-1

Active Comparator group

Description:

4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1

Treatment:

Other: IIGI+GIP+GLP-1

Other: OGTT

Other: IIGI+GIP

Other: IIGI+NaCl (placebo)

Other: IIGI+GLP-1

50 g OGTT

Other group

Description:

50 g oral glucose tolerance test (OGTT)

Treatment:

Other: IIGI+GIP+GLP-1

Other: OGTT

Other: IIGI+GIP

Other: IIGI+NaCl (placebo)

Other: IIGI+GLP-1