GLP-1 Receptor Agonist Use and Kidney Outcomes in Patients with Cancer and Type 2 Diabetes: Real-World Global Matched Cohort Analysis

Background: Renal complications are a leading cause of morbidity and mortality in cancer patients with type 2 diabetes (T2DM). Although GLP-1 agonists have established renal benefits in T2DM, their effectiveness in oncology populations remains uncertain. We assessed renal and related outcomes in cancer patients with T2DM treated with GLP-1 agonists compared to non-users. Methods: We performed a retrospective propensity score-matched analysis using the TriNetX Global Network. Adults with active cancer and T2DM prescribed semaglutide, dulaglutide, or tirzepatide (n=15,497) were matched 1:1 to similar patients not receiving GLP-1 agonists. Outcomes were ascertained up to five years post-index, excluding patients with prior events. Primary outcomes included acute kidney injury (AKI), dialysis, eGFR <30 mL/min/1.73m2, BUN >40 mg/dL, and blood transfusion. Secondary outcomes were fatigue, peripheral neuropathy, hospitalization, outpatient visits, and all-cause mortality. Hazard ratios (HR) and p-values were calculated. Results: GLP-1 agonist use was associated with lower risks of all renal outcomes: AKI occurred in 13.2% of users versus 21.7% of non-users (HR 0.64, p<0.001), dialysis in 1.1% versus 2.4% (HR 0.45, p<0.001), eGFR <30 in 5.3% versus 11.1% (HR 0.49, p<0.001), and BUN >40 in 11.1% versus 18.5% (HR 0.62, p<0.001). Blood transfusions occurred in 3.1% versus 8.7% (HR 0.36, p<0.001). Fatigue was reported in 18.4% of users and 26.6% of non-users (HR 0.71, p<0.001), peripheral neuropathy in 4.7% versus 7.6% (HR 0.65, p<0.001), hospitalization in 23.3% versus 32.9% (HR 0.74, p<0.001), and outpatient visits in 46.2% versus 55.4% (HR 0.85, p<0.001). All-cause mortality was 10.9% for GLP-1 agonist users versus 31.1% for non-users (HR 0.37, p<0.001). Conclusion: In this large, global cohort, GLP-1 agonist use in cancer patients with T2DM was associated with substantial reductions in renal complications, health care utilization, and mortality. These findings support consideration of GLP-1 agonists to improve renal and clinical outcomes in oncology patients with diabetes.