Exposure to Glucagon-Like Peptide 1 Receptor Agonists Does Not Increase the Risk of AKI Associated with Anticancer Therapy

Background: Glucagon-like peptide-1-receptor agonists (GLP-1RA) are increasingly prescribed for patients with type 2 diabetes mellitus (T2D) and congestive heart failure (CHF). Notably, reports of GLP-1RA associated acute kidney injury (AKI) have emerged. However, the risk of GLP-1RA-associated AKI among patients on anti-cancer therapies remains unknown. Considering the vulnerability of patients with cancer to acquire AKI during administration of chemotherapy, we hypothesized that exposure to GLP-1RA may further increase the risk of AKI. Methods: We conducted a retrospective review of medical records extracting cases of patients treated with anti-cancer therapies (cytotoxic, eg, alkylating agents, anti-metabolites; targeted therapy, eg, anti-VEGF, TKI; immunotherapy, eg, ICPI) over a 1-year period and were additionally exposed to a GLP-1RA during the same time period. AKI was defined per KDIGO criteria. Diagnosis of AKI was captured during the first 90 days of GLP-1RA exposure by using ICD codes. To assess the association of GLP-1RA and AKI risk, we conducted a logistic regression model including age, gender, CHF, T2D, chronic kidney disease (CKD) and anti-cancer therapy class. Results: A total of 14,783 patients were included in the study. Mean age was 67 years, 64% women, 24% had T2D, 8% CHF and 13% had CKD. Nine percent were treated with a GLP-1RA. AKI occurred in 7.2% (92/1278) of those exposed to GLP-1RA versus 6.4% (862/13505) of those with no GLP-1RA exposure (p=0.25). By univariate logistic regression analysis, exposure to GLP-1RA was associated with an OR 1.14 (95% CI 0.91-1.42; p=0.25) for AKI, whereas CKD had an OR 7.26 (95% CI 6.29, 8.29, p<0.0001), CHF an OR 4.92 (95% CI 4.19, 5.76; p<0.0001), T2D an OR 2.36 (95% CI 2.06, 2.70, p<0.0001), targeted therapy an OR 2.84 (95% CI 2.49-3.24, p<0.0001), immunotherapy an OR 2.21 (95% CI 1.55, 3.14, p<0.0001) and cytotoxic chemotherapy an OR 1.89 (95% C1 1.65, 2.17, p<0.0001). Conclusion: Contrary to our hypothesis, our data suggest that exposure to GLP-1RA is not associated with an increased risk of AKI in patients receiving anti-cancer therapies. Given the cardiovascular and anti-diabetic benefits of GLP-IRA, we suggest that these agents can be safely continued during administration of anti-cancer therapy.