Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 Receptor Agonist Dulaglutide
Abstract
OBJECTIVE: To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials. RESEARCH DESIGN AND METHODS: A total of 6,005 patients with type 2 diabetes participated (dulaglutide group N = 4,006 [dose range 0.1–3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine] N = 1,541; placebo group N = 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks. The following events were adjudicated: investigator-reported pancreatitis, adverse events (AEs) of severe or serious abdominal pain of unknown etiology, and confirmed asymptomatic increases in pancreatic enzymes ≥3× the upper limit of normal range. RESULTS: Overall, 203 events from 151 patients underwent adjudication (dulaglutide group n = 108; comparator group including placebo n = 43). Acute pancreatitis was confirmed by adjudication in seven patients (dulaglutide n = 3, placebo n = 1, sitagliptin n = 3). Exposure-adjusted incidence rates were as follows: dulaglutide group 0.85 patients/1,000 patient-years, placebo group 3.52 patients/1,000 patient-years, sitagliptin group 4.71 patients/1,000 patient-years. No events of pancreatitis were confirmed by adjudication in patients treated with exenatide twice daily, metformin, or glargine. Increases in median values of lipase and pancreatic amylase within the normal range were observed with all treatments except glargine. These changes were not associated with AEs. CONCLUSIONS: The exposure-adjusted incidence rate of acute pancreatitis in dulaglutide-treated patients was similar to the rates with placebo, with few reported cases during the entire program.
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Initial concerns regarding a possible link between GLP-1 RAs and the development of pancreatitis or pancreatic cancer have not been supported by the results of RCTs or real-world data.
“Initial concerns regarding the possible link between the use of GLP-1 RAs and the development of pancreatitis or pancreatic cancer have not been supported by the results of RCTs [53,54], or real-world data [29,55,56].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [54]
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GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art
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Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning
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“Initial concerns regarding the possible link between the use of GLP-1 RAs and the development of pancreatitis or pancreatic cancer have not been supported by the results of RCTs [53,54], or real-world data [29,55,56].”
- Authors
- Nauck, M. A., Frossard, J.-L., Barkin, J. S., Anglin, G., Hensley, I. E., Harper, K. D., & Milicevic, Z.
- Affiliations
- St. Josef-Hospital (DE)
- University Hospital of Geneva (CH)
- University of Miami (US)
- Eli Lilly (Canada) (CA)
- Eli Lilly (United States) (US)
- Eli Lilly and Company, Vienna, Austria
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2017-03-10
- Volume
- 40
- Issue
- 5
- Pages
- 647-654
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2594728560
- Cited by
- 36
- References
- 8
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 3
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- dulaglutide, acute pancreatitis, GLP-1 receptor agonists, type 2 diabetes, pancreatic enzymes, lipase, amylase, sitagliptin, exenatide, metformin, insulin glargine, drug safety
- MeSH terms
- Sitagliptin Phosphate, Insulin Glargine, Exenatide, Glucagon-Like Peptide-1 Receptor Agonists, Acute Disease, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Female, Humans, Hypoglycemic Agents, Immunoglobulin Fc Fragments, Male, Metformin, Middle Aged, Pancreatitis, Peptides, Recombinant Fusion Proteins, Venoms
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