Clinical trial NCT02598791: GIP/GLP-1 Co-Activity in Subjects With Obesity: Lowering of Food Intake
Official title: GIP/GLP-1 Co-Activity in Subjects With Obesity: Lowering of Food Intake
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Adiposity
Type 2 Diabetes
Keywords: incretin hormones
GIP
GLP-1
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2015-11-06
Enrollment: 18
Sex: MALE
Minimum age (years): 25
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: food intake
timeFrame: 250-280 min
Secondary outcomes:
measure: hunger
timeFrame: measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
measure: satiety
timeFrame: measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
measure: Fullness
timeFrame: measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
measure: Prospective food consumption
timeFrame: measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
measure: resting energy expenditure (REE)
timeFrame: -15 to 0 min. and 210 to 225 min.
measure: Insulin
timeFrame: -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min
measure: C-peptide level
timeFrame: -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min
measure: glucagon levels
timeFrame: -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min
measure: Cholesterol and FFA
timeFrame: -30, 0, 30, 60, 90, 120, 180, 240 min
measure: C-terminal cross-linked telopeptide of bone collagen (CTX)
timeFrame: -30, 0, 30, 60, 90, 120, 180, 240 min
measure: procollagen type 1 N-terminal propeptide (P1NP)
timeFrame: -30, 0, 30, 60, 90, 120, 180, 240 min
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Diabetesresearch, Gentofte hospital
Study officials:
affiliation: Center for Diabetesresearch, Gentofte Hospital, University of Copenhagen, Denmark
name: Natasha C Bergmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Bergmann NC, Lund A, Gasbjerg LS, Jorgensen NR, Jessen L, Hartmann B, Holst JJ, Christensen MB, Vilsboll T, Knop FK. Separate and Combined Effects of GIP and GLP-1 Infusions on Bone Metabolism in Overweight Men Without Diabetes. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2953-2960. doi: 10.1210/jc.2019-00008.
citation: Bergmann NC, Lund A, Gasbjerg LS, Meessen ECE, Andersen MM, Bergmann S, Hartmann B, Holst JJ, Jessen L, Christensen MB, Vilsboll T, Knop FK. Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study. Diabetologia. 2019 Apr;62(4):665-675. doi: 10.1007/s00125-018-4810-0. Epub 2019 Jan 25.