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01-04-2019 | Insulins | Article

Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study

Authors: Natasha C. Bergmann, Asger Lund, Lærke S. Gasbjerg, Emma C. E. Meessen, Maria M. Andersen, Sigrid Bergmann, Bolette Hartmann, Jens J. Holst, Lene Jessen, Mikkel B. Christensen, Tina Vilsbøll, Filip K. Knop

Published in: Diabetologia | Issue 4/2019

Abstract

Aims/hypothesis

Glucagon-like peptide 1 (GLP-1) reduces appetite and energy intake in humans, whereas the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), seems to have no effect on eating behaviour. Interestingly, studies in rodents have shown that concomitant activation of GIP and GLP-1 receptors may potentiate the satiety-promoting effect of GLP-1, and a novel dual GLP-1/GIP receptor agonist was recently shown to trigger greater weight losses compared with a GLP-1 receptor agonist in individuals with type 2 diabetes. The aim of this study was to delineate the effects of combined GIP and GLP-1 receptor activation on energy intake, appetite and resting energy expenditure in humans.

Methods

We examined 17 overweight/obese men in a crossover design with 5 study days. On day 1, a 50 g OGTT was performed; on the following 4 study days, the men received an isoglycaemic i.v. glucose infusion (IIGI) plus saline (154 mmol/l NaCl; placebo), GIP (4 pmol kg⁻¹ min⁻¹), GLP-1 (1 pmol kg⁻¹ min⁻¹) or GIP+GLP-1 (4 and 1 pmol kg⁻¹ min⁻¹, respectively). All IIGIs were performed in a randomised order blinded for the participant and the investigators. The primary endpoint was energy intake as measured by an ad libitum meal after 240 min. Secondary endpoints included appetite ratings and resting energy expenditure, as well as insulin, C-peptide and glucagon responses.

Results

Energy intake was significantly reduced during IIGI+GLP-1 compared with IIGI+saline infusion (2715 ± 409 vs 4483 ± 568 kJ [mean ± SEM, n = 17], p = 0.014), whereas there were no significant differences in energy intake during IIGI+GIP (4062 ± 520 kJ) or IIGI+GIP+GLP-1 (3875 ± 451 kJ) infusion compared with IIGI+saline (p = 0.590 and p = 0.364, respectively). Energy intake was higher during IIGI+GIP+GLP-1 compared with IIGI+GLP-1 infusion (p = 0.039).

Conclusions/interpretation

While GLP-1 infusion lowered energy intake in overweight/obese men, simultaneous GIP infusion did not potentiate this GLP-1-mediated effect.

Trial registration

ClinicalTrials.gov NCT02598791

Funding

This study was supported by grants from the Innovation Fund Denmark and the Vissing Foundation.

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Title: Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study
Authors: Natasha C. Bergmann
Asger Lund
Lærke S. Gasbjerg
Emma C. E. Meessen
Maria M. Andersen
Sigrid Bergmann
Bolette Hartmann
Jens J. Holst
Lene Jessen
Mikkel B. Christensen
Tina Vilsbøll
Filip K. Knop
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Keywords: Insulins
Overweight
Insulins
Published in: Diabetologia / Issue 4/2019
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-018-4810-0

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Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Trial registration

Funding

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Conclusions/interpretation

Trial registration

Funding

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