Risk of Pancreatitis With Incretin Therapies Versus Thiazolidinediones in the Veterans Health Administration
Abstract
Background: Incretin therapies, comprised of the dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have been increasingly utilized for the treatment of type 2 diabetes (T2DM). Previous studies have conflicting results regarding risk of pancreatitis associated with these agents—some suggest an increased risk and others find no correlation. Adverse event reporting systems indicate that incretin therapies are some of the most common drugs associated with reports of pancreatitis. Objectives: This study aimed to compare the odds of developing pancreatitis in veterans with T2DM prescribed an incretin therapy versus thiazolidinediones (TZDs: pioglitazone and rosiglitazone) within the Veterans Health Administration (VHA). Methods: This was a retrospective cohort study analyzing veterans with T2DM first prescribed an incretin therapy or a TZD between January 1, 2011, and December 31, 2021. A diagnosis of pancreatitis within 365 days of being prescribed either therapy was counted as a positive case. Data was collected and analyzed utilizing VA’s Informatics and Computing Infrastructure (VINCI) and an adjusted odds ratio was calculated. Results: The TZD cohort consisted of 42 912 patients compared with the incretin cohort of 304 811 patients. The TZD cohort had a pancreatitis incidence rate of 1.94 cases per 1000 patients. The incretin cohort had a incidence rate of 2.06 cases per 1000 patients. An adjusted odds ratio found no statistical difference of pancreatitis cases between the TZD and incretin cohorts (adjusted odds ratio [AOR] = 0.94, 95% CI [0.75, 1.18]). Conclusion and Relevance: This retrospective cohort study of national VHA data found a relatively low incidence of pancreatitis in both cohorts, and an adjusted odds ratio found no statistical difference of pancreatitis in patients prescribed an incretin therapy compared with a control group. This data adds to growing evidence that incretin therapies do not seem to be associated with an increased risk of developing pancreatitis.
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In the Veterans Health Administration national dataset, adjusted OR indicated no significant difference in pancreatitis occurrences between thiazolidinedione and incretin groups (adjusted OR 0.94; 95% CI 0.75 to 1.18).
“In the Veterans Health Administration (VHA) national dataset, an adjusted OR indicated no significant difference in pancreatitis occurrences between thiazolidinedione and incretin groups (adjusted OR, 0.94; 95% CI, 0.75 to 1.18) [56].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [56]
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 [56]
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Lebovitz, H. E. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1270-y · Cited by 388 · see citing works
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Sheahan, K. H., Wahlberg, E. A., & Gilbert, M. P. (2020) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2019-137186 · Cited by 194 · see citing works
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Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity
Drucker, D. J. (2024) · Diabetes Care · doi:10.2337/dci24-0003 · Cited by 383 · see citing works
Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning
Kim, J. A., & Yoo, H. J. (2025) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0242 · Cited by 71 · see citing works
“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].”
Influential
- Authors
- Wilhite, K., Reid, J. M., & Lane, M.
- Affiliations
- Veterans Health Administration (US)
- Lexington VA Health Care System (US)
- Corresponding author
- Wilhite, Kristen
- Venue
- Annals of Pharmacotherapy
- Publisher
- SAGE Publications
- Published
- 2023-10-26
- Volume
- 58
- Issue
- 7
- Pages
- 685-689
- ISSN
- 0012-6578 (ISSN-L)
- 1060-0280
- 1542-6270
- OpenAlex
- W4387950671
- Cited by
- 12
- References
- 4
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- pancreatitis, incretin-based therapy, thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, type 2 diabetes, pioglitazone, rosiglitazone, adverse drug reactions, veterans, drug safety
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Rosiglitazone, Pioglitazone, Glucagon-Like Peptide-1 Receptor Agonists, Aged, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Pancreatitis, Retrospective Studies, United States, United States Department of Veterans Affairs, Veterans, Cohort Studies, Thiazolidinediones, Incretins, Dipeptidyl-Peptidase IV Inhibitors
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