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

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

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.

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.

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