Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study
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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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The additive effect of simultaneous GLP-1 and GIP receptor activation on food intake and glycaemia was not observed in some acute clinical studies.
“despite that this additive effect in food intake and glycaemia was not observed in some acute clinical studies [41, 42].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [42]
The Discussion (page unavailable) reports that GIP and GLP-1 co-infusion did not lower energy intake more than GLP-1 alone in overweight/obese men. The study maintained isoglycaemic conditions, so it did not directly test whether co-infusion provided an additive improvement in glycaemia; the Results report similar amounts of glucose infused with GLP-1 alone and with co-infusion. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn a study of 17 overweight or obese males, GIP alone had no effect on energy intake.
“Seventeen overweight or obese males were given either GIP or GLP-1 alone for 5 days, or GIP+GLP-1 at the same time, and allowed to eat ad libitum food 240 min later, and there was no effect on energy intake in the GIP group.”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [68]
In the same study, combined GIP+GLP-1 administration increased energy intake more than GLP-1 alone (P = 0.039).
“Energy intake decreased in the GLP-1 administration group, but energy intake increased more in the GIP+GLP-1 combination administration group (P = 0.039) [68].”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [68]
In the same study, GLP-1 administration decreased energy intake.
“Energy intake decreased in the GLP-1 administration group, but energy intake increased more in the GIP+GLP-1 combination administration group (P = 0.039) [68].”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [68]
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Novel GLP-1-based Medications for Type 2 Diabetes and Obesity
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- Authors
- Bergmann, N. C., Lund, A., Gasbjerg, L. S., Meessen, E. C. E., Andersen, M. M., Bergmann, S., Hartmann, B., Holst, J. J., Jessen, L., Christensen, M. B., Vilsbøll, T., & Knop, F. K.
- Affiliations
- University of Copenhagen (DK)
- Amsterdam UMC Location University of Amsterdam (NL)
- Gentofte Hospital (DK)
- Zealand Pharma (Denmark) (DK)
- Corresponding author
- Knop, Filip K.
- ORCID
- Venue
- Diabetologia
- Published
- 2019-01-25
- Volume
- 62
- Issue
- 4
- Pages
- 665-675
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2911644854
- Cited by
- 142
- References
- 38
- Citations by year
- 2026: 9 · 2025: 28 · 2024: 19 · 2023: 17 · 2022: 19 · 2021: 22 · 2020: 13 · 2019: 14
- FWCI
- 9.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- The Vissing Foundation
- The Innovation Fund Denmark
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, GIP/GLP-1 receptor agonist, energy intake, appetite, resting energy expenditure, incretins, satiety, obesity, overweight
- MeSH terms
- Adult, Aged, Appetite, Blood Glucose, Energy Intake, Calorimetry, Double-Blind Method, Energy Metabolism, Gastric Inhibitory Polypeptide, Glucagon, Humans, Insulin, Male, Middle Aged, Obesity, Weight Loss, Cross-Over Studies, Overweight, Glucagon-Like Peptide 1
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