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

NCT ID: NCT02598791

Last Updated: 2018-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-01

Study Completion Date

2016-06-20

Brief Summary

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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

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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.

Conditions

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Obesity Adiposity Type 2 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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IIGI+GIP

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

Group Type ACTIVE_COMPARATOR

IIGI+GIP

Intervention Type OTHER

Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia

IIGI+GLP-1

Intervention Type OTHER

glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia

IIGI+NaCl (placebo)

Intervention Type OTHER

i.v. NaCl during isoglycemia

OGTT

Intervention Type OTHER

50 g oral glucose tolerance test

IIGI+GIP+GLP-1

Intervention Type OTHER

i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia

IIGI+GLP-1

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

Group Type ACTIVE_COMPARATOR

IIGI+GIP

Intervention Type OTHER

Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia

IIGI+GLP-1

Intervention Type OTHER

glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia

IIGI+NaCl (placebo)

Intervention Type OTHER

i.v. NaCl during isoglycemia

OGTT

Intervention Type OTHER

50 g oral glucose tolerance test

IIGI+GIP+GLP-1

Intervention Type OTHER

i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia

IIGI+NaCl (placebo)

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

Group Type PLACEBO_COMPARATOR

IIGI+GIP

Intervention Type OTHER

Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia

IIGI+GLP-1

Intervention Type OTHER

glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia

IIGI+NaCl (placebo)

Intervention Type OTHER

i.v. NaCl during isoglycemia

OGTT

Intervention Type OTHER

50 g oral glucose tolerance test

IIGI+GIP+GLP-1

Intervention Type OTHER

i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia

IIGI+GIP+GLP-1

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

Group Type ACTIVE_COMPARATOR

IIGI+GIP

Intervention Type OTHER

Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia

IIGI+GLP-1

Intervention Type OTHER

glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia

IIGI+NaCl (placebo)

Intervention Type OTHER

i.v. NaCl during isoglycemia

OGTT

Intervention Type OTHER

50 g oral glucose tolerance test

IIGI+GIP+GLP-1

Intervention Type OTHER

i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia

50 g OGTT

50 g oral glucose tolerance test (OGTT)

Group Type OTHER

IIGI+GIP

Intervention Type OTHER

Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia

IIGI+GLP-1

Intervention Type OTHER

glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia

IIGI+NaCl (placebo)

Intervention Type OTHER

i.v. NaCl during isoglycemia

OGTT

Intervention Type OTHER

50 g oral glucose tolerance test

IIGI+GIP+GLP-1

Intervention Type OTHER

i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia

Interventions

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IIGI+GIP

Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia

Intervention Type OTHER

IIGI+GLP-1

glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia

Intervention Type OTHER

IIGI+NaCl (placebo)

i.v. NaCl during isoglycemia

Intervention Type OTHER

OGTT

50 g oral glucose tolerance test

Intervention Type OTHER

IIGI+GIP+GLP-1

i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

25 Years

Maximum Eligible Age

70 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role lead

Responsible Party

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Natasha Chidekel Bergmann

MD Ph.D student

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Natasha C Bergmann, MD

Role: PRINCIPAL_INVESTIGATOR

Center for Diabetesresearch, Gentofte Hospital, University of Copenhagen, Denmark

Locations

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Center for Diabetesresearch, Gentofte hospital

Hellerup, , Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type DERIVED
PMID: 30848791 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30683945 (View on PubMed)

Finan B, Ma T, Ottaway N, Muller TD, Habegger KM, Heppner KM, Kirchner H, Holland J, Hembree J, Raver C, Lockie SH, Smiley DL, Gelfanov V, Yang B, Hofmann S, Bruemmer D, Drucker DJ, Pfluger PT, Perez-Tilve D, Gidda J, Vignati L, Zhang L, Hauptman JB, Lau M, Brecheisen M, Uhles S, Riboulet W, Hainaut E, Sebokova E, Conde-Knape K, Konkar A, DiMarchi RD, Tschop MH. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci Transl Med. 2013 Oct 30;5(209):209ra151. doi: 10.1126/scitranslmed.3007218.

Reference Type BACKGROUND
PMID: 24174327 (View on PubMed)

Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013 Jun 4;17(6):819-837. doi: 10.1016/j.cmet.2013.04.008. Epub 2013 May 16.

Reference Type BACKGROUND
PMID: 23684623 (View on PubMed)

Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest. 1998 Feb 1;101(3):515-20. doi: 10.1172/JCI990.

Reference Type BACKGROUND
PMID: 9449682 (View on PubMed)

Nissen A, Christensen M, Knop FK, Vilsboll T, Holst JJ, Hartmann B. Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans. J Clin Endocrinol Metab. 2014 Nov;99(11):E2325-9. doi: 10.1210/jc.2014-2547. Epub 2014 Aug 21.

Reference Type BACKGROUND
PMID: 25144635 (View on PubMed)

Other Identifiers

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H-15008790 (GASOLIN)

Identifier Type: -

Identifier Source: org_study_id

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