Evaluation of the impact of GLP-1 receptor agonists (RAs) on stage of PDAC diagnosis: A retrospective matched cohort study.

Abstract

e16462 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that is most frequently diagnosed at either the locally advanced or metastatic setting. Most patients will not have the opportunity for curative-intent surgical resection. The early symptoms of pancreatic cancer, including weight loss, early satiety, and back and/or abdominal pain, provide clinical clues that can trigger a medical evaluation and diagnosis of PDAC. GLP-1 (glucagon-like peptide-1) receptor agonists (RAs) are widely used for type 2 diabetes and obesity management. However, the side effects of GLP-1 RAs include early satiety, diarrhea, and weight loss. This potential overlap in drug effects and cancer symptoms raises the question of delayed PDAC diagnosis in patients on GLP-1 RAs. We conducted a retrospective matched cohort study of patients diagnosed with PDAC to evaluate whether GLP1 RAs were associated with a later stage of diagnosis. Methods: Eighty-eight patients with PDAC on a GLP-1 RA at the time of diagnosis were matched 2:1 by age, ECOG status, and diagnosis date to 176 patients with PDAC who were not on a GLP-1 RA at the time of diagnosis. Extensive clinical information was gathered, including stage at diagnosis [resectable, borderline resectable (BRPC), locally advanced (LAPC), or metastatic (mPDAC)], diagnosis of diabetes, treatments, and outcomes. Risks of diagnosis at each stage were estimated using multinomial logistic regression. Results: GLP-1 RA users had 21.7 percentage point higher risk of diagnosis with BRPC than resectable PDAC, as compared to non-GLP-1 RA users (p = .035), and were 12.0 and 12.5 percentage points more likely to be diagnosed as LAPC or mPDAC than resectable disease, respectively. After weighting adjustment for diabetes mellitus diagnosis, GLP-1 RA users were 18.6 percentage points more likely to be diagnosed with BRPC vs. resectable disease (p = 0.09). 39% of non-GLP-1 RA users underwent curative-intent surgical resection compared to 27% of users (p = 0.065). Conclusions: In this small retrospective matched cohort study, we observed that patients who were taking GLP-1 RA agonists at the time of PDAC diagnosis were more likely to be diagnosed with non-resectable disease compared to a matched group of patients who were not taking GLP-1 RAs. This observation may be due to an overlap in symptoms between GLP-1 RA and PDAC, leading clinicians to attribute satiety and weight loss to the agent. Clinicians should be attentive to the symptoms of patients on GLP-1 RAs, particularly if symptoms are out of proportion to what is expected with the use of this drug class. Stage Difference in risk differences (GLP-1 minus non-GLP-1) Std. Err. p-value BRPC vs. resectable 0.217 0.080 0.035 LAPC vs. resectable 0.120 0.087 0.217 mPDAC vs. resectable 0.125 0.101 0.263