---
title: "GLP-1 Receptor Agonists and Long-Term Pancreatic Cancer Risk: TriNetX Propensity-Matched Analysis"
id: "pubmed-42745130"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42745130"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42745130/"
doi: "10.1007/s12029-026-01523-w"
published_at: "2026-09-16T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# GLP-1 Receptor Agonists and Long-Term Pancreatic Cancer Risk: TriNetX Propensity-Matched Analysis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42745130
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42745130/)
- **DOI:** [10.1007/s12029-026-01523-w](https://doi.org/10.1007%2Fs12029-026-01523-w)
- **Published At:** 2026-09-16T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This retrospective new-user cohort study used the **TriNetX** global federated electronic health record network to evaluate whether initiation of **GLP-1 receptor agonists (GLP-1 RAs)** is associated with incident **pancreatic cancer** in adults with type 2 diabetes mellitus (T2DM). - Investigators performed six separate 1:1 propensity score–matched comparisons of new GLP-1 RA users versus new users of insulin, metformin, DPP-4 inhibitors, SGLT2 inhibitors, sulfonylureas, and thiazolidinediones, matching on 39 baseline covariates (demographics, comorbidities, procedures, medication exposures). - The primary outcome was incident pancreatic cancer (ICD-10-CM C25) occurring between 365 and 7,300 days after the index prescription; hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazards models. - Compared with insulin users, GLP-1 RA users had a lower hazard of pancreatic cancer (HR 0.43, 95% CI 0.35–0.53); absolute risks after matching were reported (GLP-1 RA 0.15% vs insulin 0.11%; absolute risk difference 0.04 percentage points). - Versus metformin, sulfonylureas, thiazolidinediones, and DPP-4 inhibitors, GLP-1 RA users had significantly lower hazards of pancreatic cancer (metformin HR 1.39; sulfonylureas HR 1.37; thiazolidinediones HR 1.30; DPP-4i HR 1.31), with small absolute risk differences listed in the abstract. - No significant difference in pancreatic cancer hazard was observed between GLP-1 RA users and SGLT2 inhibitor users (HR 1.08, 95% CI 0.87–1.34). - The study concludes the association between **GLP-1 RA** use and pancreatic cancer risk varied by comparator agent: lower hazard compared with several oral agents and DPP-4i and SGLT2i (no difference), but higher hazard relative to insulin in this analysis. - The abstract reports matching on 39 covariates and the analytic window for incident cancer; other methodological details, such as exact cohort sizes after matching, censoring procedures, and sensitivity analyses, were not reported in the abstract and therefore are not available from the provided source text.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Anne Arundel Medical Center, Annapolis, MD, USA. * 2 Aga Khan University Karachi, Karachi, Pakistan. * 3 Dow University of Health Sciences, Karachi, Pakistan. * 4 Department of Gastroenterology, University of Pittsburgh Medical Center, Pittsburg, PA, USA. qureshiia@upmc.edu. * 5 Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA. * 6 Geisinger Health System, Danville, PA, USA. * 7 Division of Gastroenterology and Hepatology, University of California, Davis, CA, USA. * 8 Division of Gastroenterology and Hepatology, TidalHealth Peninsula Regional Medical Center, Salisbury, MD, USA. * PMID: **42745130** * DOI: [ 10.1007/s12029-026-01523-w ](https://doi.org/10.1007/s12029-026-01523-w) Item in Clipboard # Long-Term Association Between GLP-1 Receptor Agonist Use and Incident Pancreatic Cancer: A Propensity Score-Matched Retrospective Cohort Study Using the TriNetX Network Muhammad Ali Ibrahim Kazi et al. J Gastrointest Cancer. 2026. Show details Display options Display options Format Abstract PubMed PMID J Gastrointest Cancer Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Gastrointest+Cancer%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Gastrointest+Cancer%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42745130/) . 2026 Sep 16;57(1):221. doi: 10.1007/s12029-026-01523-w. ### Authors [Muhammad Ali Ibrahim Kazi](https://pubmed.ncbi.nlm.nih.gov/?term=Kazi+MAI&cauthor_id=42745130)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-1 "Anne Arundel Medical Center, Annapolis, MD, USA."), [Junaid Khan](https://pubmed.ncbi.nlm.nih.gov/?term=Khan+J&cauthor_id=42745130)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-1 "Anne Arundel Medical Center, Annapolis, MD, USA."), [Syed Musa Mufarrih](https://pubmed.ncbi.nlm.nih.gov/?term=Mufarrih+SM&cauthor_id=42745130)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-2 "Aga Khan University Karachi, Karachi, Pakistan."), [Maham Siddiqui](https://pubmed.ncbi.nlm.nih.gov/?term=Siddiqui+M&cauthor_id=42745130)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-1 "Anne Arundel Medical Center, Annapolis, MD, USA."), [Huzaifa Ul Haque Ansari](https://pubmed.ncbi.nlm.nih.gov/?term=Ansari+HUH&cauthor_id=42745130)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-3 "Dow University of Health Sciences, Karachi, Pakistan."), [Muhammad Ahmed](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmed+M&cauthor_id=42745130)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-3 "Dow University of Health Sciences, Karachi, Pakistan."), [Imran Qureshi](https://pubmed.ncbi.nlm.nih.gov/?term=Qureshi+I&cauthor_id=42745130)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-4 "Department of Gastroenterology, University of Pittsburgh Medical Center, Pittsburg, PA, USA. qureshiia@upmc.edu."), [Abdulhameed Al-Sabban](https://pubmed.ncbi.nlm.nih.gov/?term=Al-Sabban+A&cauthor_id=42745130)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-5 "Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA."), [Nihaal Prashant Karnik](https://pubmed.ncbi.nlm.nih.gov/?term=Karnik+NP&cauthor_id=42745130)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-6 "Geisinger Health System, Danville, PA, USA."), [Andrew Gilman](https://pubmed.ncbi.nlm.nih.gov/?term=Gilman+A&cauthor_id=42745130)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-7 "Division of Gastroenterology and Hepatology, University of California, Davis, CA, USA."), [Sanmeet Singh](https://pubmed.ncbi.nlm.nih.gov/?term=Singh+S&cauthor_id=42745130)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-1 "Anne Arundel Medical Center, Annapolis, MD, USA."), [Andrew Canakis](https://pubmed.ncbi.nlm.nih.gov/?term=Canakis+A&cauthor_id=42745130)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42745130/#short-view-affiliation-8 "Division of Gastroenterology and Hepatology, TidalHealth Peninsula Regional Medical Center, Salisbury, MD, USA.") ### Affiliations * 1 Anne Arundel Medical Center, Annapolis, MD, USA. * 2 Aga Khan University Karachi, Karachi, Pakistan. * 3 Dow University of Health Sciences, Karachi, Pakistan. * 4 Department of Gastroenterology, University of Pittsburgh Medical Center, Pittsburg, PA, USA. qureshiia@upmc.edu. * 5 Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA. * 6 Geisinger Health System, Danville, PA, USA. * 7 Division of Gastroenterology and Hepatology, University of California, Davis, CA, USA. * 8 Division of Gastroenterology and Hepatology, TidalHealth Peninsula Regional Medical Center, Salisbury, MD, USA. * PMID: **42745130** * DOI: [ 10.1007/s12029-026-01523-w ](https://doi.org/10.1007/s12029-026-01523-w) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes mellitus (T2DM) and obesity. Whether GLP-1 RA use is associated with altered long-term pancreatic cancer risk remains uncertain, with conflicting evidence from prior observational studies. We aimed to evaluate the association between initiation of GLP-1 RA therapy and incident pancreatic cancer risk compared with six classes of antidiabetic agents. **Methods:** We conducted a retrospective, new-user cohort study using the TriNetX global federated electronic health record network. Adults with T2DM initiating GLP-1RA therapy were compared with incident users of insulin, metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones in six separate propensity score-matched analyses (1:1, greedy nearest-neighbor algorithm, caliper 0.1 pooled standard deviations). Matching was performed on 39 baseline covariates,, including demographics, comorbidities, procedures, and medication exposures. The primary outcome was incident pancreatic cancer (ICD-10-CM C25) occurring between 365 and 7,300 days after the index prescription. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. **Results:** After propensity score matching, GLP-1 RA users compared with insulin users had a lower hazard of pancreatic cancer (HR 0.43, 95% CI 0.35, 0.53; absolute risk: GLP-1 RA 0.15% vs. insulin 0.11%; absolute risk difference [ARD] 0.04% points). In contrast, users of metformin (HR 1.39, 95% CI 1.16, 1.66; ARD 0.04% points), sulfonylureas (HR 1.37, 95% CI 1.13, 1.65; ARD 0.07% points), thiazolidinediones (HR 1.30, 95% CI 1.001, 1.678; ARD 0.15% points) and DPP-4i (HR 1.31; 95% CI 1.06, 1.61; ARD 0.08% points) had significantly higher hazards of pancreatic cancer compared with GLP-1 RA users. No significant difference was observed between GLP-1 RA users and users of SGLT2 inhibitors (HR 1.08, 95% CI 0.87, 1.34). **Conclusions:** In this large, real-world, propensity score-matched analysis, the direction and magnitude of the association between GLP-1 RA use and pancreatic cancer risk varied by comparator agent. GLP-1 RA use was associated with a lower hazard of pancreatic cancer relative to metformin, sulfonylureas, thiazolidinediones, and DPP-4i while no significant difference relative to SGLT2i, and a higher hazard relative to insulin. **Keywords:** GLP-1 receptor agonists; Incretin therapy; Pancreatic cancer; Pharmacoepidemiology; Propensity score matching; TriNetX; Type 2 diabetes mellitus. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Competing interests: The authors declare no competing interests. ## References 1. 1. Makhoul I, Yacoub A, Siegel E. Type 2 diabetes mellitus is associated with increased risk of pancreatic cancer: A veteran administration registry study. SAGE Open Med. 2016;4:2050312116682257. - [DOI](https://doi.org/10.1177/2050312116682257) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/28348740/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/5354175/) 2. 1. Pannala R, Leirness JB, Bamlet WR, Basu A, Petersen GM, Chari ST. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology. 2008;134(4):981–7. . - [DOI](https://doi.org/10.1053/j.gastro.2008.01.039) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/18395079/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/2323514/) 3. 1. Bao B, Wang Z, Li Y, et al. The complexities of obesity, diabetes, and the development and progression of pancreatic cancer. Biochim Biophys Acta. 2011;1815(2):135–46. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/21129444/) 4. 1. Chari ST, Leibson CL, Rabe KG, Timmons LJ, Ransom J, de Andrade M, Petersen GM. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology. 2008;134(1):95–101. . - [DOI](https://doi.org/10.1053/j.gastro.2007.10.040) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/18061176/) 5. 1. Salvatore T, Marfella R, Rizzo MR, Sasso FC. Pancreatic cancer and diabetes: A two-way relationship in the perspective of diabetologist. Int J Surg. 2015;21(Suppl 1):S72–7. . - [DOI](https://doi.org/10.1016/j.ijsu.2015.06.063) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/26123386/) Show all 53 references ## MeSH terms * Aged Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Aged%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Aged) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42745130/) * Diabetes Mellitus, Type 2* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitus%2C+Type+2) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42745130/) * Female Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Female) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42745130/) * Glucagon-Like Peptide-1 Receptor Agonists* Actions * [ Search in PubMed ](https://pubmed.ncbi.
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