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Cited by 125Diabetes Treatment and ManagementPancreatitis Pathology and TreatmentPancreatic and Hepatic Oncology Research

The Human GLP-1 Analog Liraglutide and the Pancreas

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Nyborg, Niels C.B., Mølck, Anne-Marie, Madsen, Lars W., Bjerre Knudsen, Lotte·2012·Diabetes
DOI 10.2337/db11-0936PMC PMC3331765
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Abstract

Glucagon-like peptide (GLP)-1 analogs have been implicated as a risk factor for pancreatitis in humans. We investigated whether liraglutide, the once-daily human GLP-1 analog, induces pancreatitis in rats, mice, and monkeys. Pancreata from mice, rats, and nonhuman primates were examined macro- and microscopically. Evaluation of preneoplastic proliferative lesions in the pancreata from nonhuman primates was performed. After 2 years of treatment, 3 of 79 male mice in the control group and 2, 1, 1, and 1 mice in the different liraglutide groups (of 67–79 mice per group) had pancreatitis based on microscopic criteria. For females, the numbers were 0 of 79 mice in the control group and 3 mice in all the liraglutide groups (of 66–76 mice per group). Pancreatitis was not the cause of death in any animals. There were no cases of pancreatitis, macroscopically or microscopically, in 400 rats. Neither pancreatitis nor preneoplastic proliferative lesions was found in monkeys dosed for 87 weeks, with plasma liraglutide exposure 60-fold higher than that observed in humans at the maximal clinical dose. In conclusion, liraglutide did not induce pancreatitis in mice, rats, or monkeys when dosed for up to 2 years and at exposure levels up to 60 times higher than in humans.

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  • The majority of animal studies did not find any effect of GLP-1RAs on pancreatic physiology, even with doses up to 240 times the normal human dose.

    “However, the majority of animal studies did not find any effect of GLP-1RAs on pancreatic physiology, even with doses up to 240 the normal human dose (73–76).”

    From Safety of Semaglutide (2021) · cites this paper as [73]

    The Discussion reports no dose-dependent pancreatitis effect in the paper’s liraglutide studies, and the nonhuman-primate Results report no histological signs of pancreatitis. But this does not establish that a majority of animal studies found no effect of GLP-1RAs on pancreatic physiology generally. The paper describes exposures up to 60 times the maximal clinical human exposure, not 240 times the human dose. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Nyborg, N. C. B., Mølck, A.-M., Madsen, L. W., & Bjerre Knudsen, L.
Affiliations
  • Novo Nordisk (Denmark) (DK)
  • Department of Diabetes and Pharmacology Management, Novo Nordisk, Bagsværd, Denmark
ORCID
Mølck, Anne-Marie
Venue
Diabetes
Publisher
American Diabetes Association
Published
2012-04-13
Volume
61
Issue
5
Pages
1243-1249
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db11-0936
PMC
PMC3331765
OpenAlex
W2115357902
Cited by
125
References
5
Citations by year
2026: 4 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 15 · 2014: 28 · 2013: 32 · 2012: 10
FWCI
21.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords
liraglutide, GLP-1 receptor agonists, pancreatitis, drug-induced pancreatitis, chronic toxicity, non-human primates, mice, rats, plasma exposure, type 2 diabetes treatment
MeSH terms
Liraglutide, Animals, Drug Administration Schedule, Female, Humans, Macaca fascicularis, Male, Pancreas, Pancreatitis, Rats, Sprague-Dawley, Mice, Rats, Glucagon-Like Peptide 1

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