Impact of glucagon-like peptide-1 receptor agonists on clinical outcomes in pancreatic cancer: A large-scale real-world cohort study.

Abstract

688 Background: Pancreatic cancer is one of the leading causes of cancer-related death and is associated with poor overall survival. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely prescribed for diabetes and obesity, have been investigated for potential impact in patients with pancreatic cancer, although their safety and clinical effects remain uncertain. This study evaluates the association between GLP-1RA use and clinical outcomes in a real-world cohort of patients with pancreatic cancer. Methods: Using the TriNetX Network database (72 healthcare organizations), we identified patients with pancreatic cancer who were prescribed GLP-1 receptor agonists (GLP-1RAs; n = 1,972) from 2010 to 2022, and matched controls without exposure to GLP-1RAs (n = 57,645). Propensity score matching balanced demographics and comorbidities, yielding 1,821 patients in each group. The primary outcomes were all-cause mortality and overall survival, assessed with Kaplan–Meier survival curves. Secondary outcomes included hospitalization, postoperative infection/sepsis, venous thromboembolism (VTE), acute kidney injury (AKI), and chronic kidney disease (CKD). Risk ratios (RRs) with 95% confidence intervals were estimated over a three-year follow-up period. Results: After propensity matching, the mean age was 72.0 years in the GLP-1RA group and 71.8 years in the non-GLP-1RA group. GLP-1RA users had lower all-cause mortality compared with non-users (40.6% vs 44.3%; risk ratio [RR] 0.92, 95% CI 0.85–0.99; p = 0.025) and longer median survival (1,065 vs 824 days; hazard ratio [HR] 0.90, 95% CI 0.81–0.997; p = 0.043). Hospitalization was less frequent in GLP-1RA users (40.2% vs 46.1%; RR 0.87; p = 0.040). Postoperative infection/sepsis (18.1% vs 21.3%; RR 0.85; p = 0.023) was also significantly lower in the GLP-1RA group. No significant differences were observed for VTE (15.1% vs 16.4%; p = 0.335), AKI (18.7% vs 20.2%; p = 0.317), or CKD (10.4% vs 8.4%; p = 0.073). Conclusions: GLP-1RA use was associated with lower mortality, longer survival, and reduced risks of hospitalization and postoperative infection/sepsis in patients with pancreatic cancer, without increased risk of VTE or renal complications. Prospective studies are warranted to confirm these findings and further clarify the role of GLP-1RAs in pancreatic cancer care.