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Cited by 80Diabetes Treatment and ManagementPancreatic function and diabetesRegulation of Appetite and Obesity

The effects of dual GLP-1/GIP receptor agonism on glucagon secretion-A Review

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Mathiesen, David S., Bagger, Jonatan I., Bergmann, Natasha C., Lund, Asger, Christensen, Mikkel B., Vilsbøll, Tina, Knop, Filip K.·2019·International Journal of Molecular Sciences
DOI 10.3390/ijms20174092PMC PMC6747202
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Abstract

The gut-derived incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted after meal ingestion and work in concert to promote postprandial insulin secretion. Furthermore, GLP-1 inhibits glucagon secretion when plasma glucose concentrations are above normal fasting concentrations while GIP acts glucagonotropically at low glucose levels. A dual incretin receptor agonist designed to co-activate GLP-1 and GIP receptors was recently shown to elicit robust improvements of glycemic control (mean haemoglobin A1c reduction of 1.94%) and massive body weight loss (mean weight loss of 11.3 kg) after 26 weeks of treatment with the highest dose (15 mg once weekly) in a clinical trial including overweight/obese patients with type 2 diabetes. Here, we describe the mechanisms by which the two incretins modulate alpha cell secretion of glucagon, review the effects of co-administration of GLP-1 and GIP on glucagon secretion, and discuss the potential role of glucagon in the therapeutic effects observed with novel unimolecular dual GLP-1/GIP receptor agonists. For clinicians and researchers, this manuscript offers an understanding of incretin physiology and pharmacology, and provides mechanistic insight into future antidiabetic and obesity treatments.

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Cited by

Sorted by citations

Authors
Mathiesen, D. S., Bagger, J. I., Bergmann, N. C., Lund, A., Christensen, M. B., Vilsbøll, T., & Knop, F. K.
Affiliations
University of Copenhagen (DK)
Corresponding author
Knop, Filip K.
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2019-08-22
Volume
20
Issue
17
Pages
4092
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms20174092
PMC
PMC6747202
OpenAlex
W2969584990
Cited by
80
References
30
Citations by year
2026: 10 · 2025: 11 · 2024: 11 · 2023: 11 · 2022: 16 · 2021: 11 · 2020: 8 · 2019: 2
FWCI
1.42
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Steno Diabetes Center Copenhagen (SDCC 3.F CMP)
  • Novo Nordisk Fonden (NNF17OC0029370, NNF17OC0027220, NNF17OC0027794)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
GIP/GLP-1 receptor agonist, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, glucagon secretion, incretins, type 2 diabetes, obesity, glycemic control, weight loss
MeSH terms
Glucagon-Like Peptide-1 Receptor Agonists, Animals, Diabetes Mellitus, Type 2, Gastric Inhibitory Polypeptide, Glucagon, Humans, Receptors, Gastrointestinal Hormone, Glucagon-Like Peptide 1

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