Antiproteinuric Effect of Sodium Glucose Transporter 2 Inhibitors in Patients with Hepatocellular Carcinoma receiving Atezolizumab plus Bevacizumab: A Multi-institutional Retrospective Study

Background Sodium glucose transporter 2 inhibitors (SGLT2i) reduce proteinuria in patients with diabetes and chronic kidney disease. This study aimed to evaluate the prophylactic effect of SGLT2i on bevacizumab-induced proteinuria. Methods This was a multi-institutional retrospective study including patients with hepatocellular carcinoma (HCC) who initiated atezolizumab plus bevacizumab between September 2020 and December 2023. The primary outcome was the time to exacerbation of proteinuria grade from baseline during the first 6 months of bevacizumab treatment according to the administration of SGLT2i. Results No significant difference in the time to exacerbation of proteinuria grade was observed between the SGLT2i ( n  = 29) and non-SGLT2i ( n  = 159) groups (the median time of SGLT2i group: 157 days vs. non-SGLT2i group: 116 days, p  = 0.95). Multivariate analysis revealed that diabetes and systolic blood pressure (sBP) ≥ 130 mmHg (hazard ratio, 2.12; 95% confidence interval, 1.14–3.95; p  = 0.018) were significantly associated with an exacerbation of proteinuria grade, whereas SGLT2i were not significantly associated with an exacerbation of proteinuria grade. Among patients with comorbidities of diabetes and sBP ≥ 130 mmHg at the initiation of bevacizumab ( n  = 27), the SGLT2i had a significantly longer time to exacerbation of proteinuria grade (the median time of SGLT2i group: 90 days vs. non-SGLT2i group: 42 days, p  = 0.016). Conclusion SGLT2i did not exert a prophylactic effect on proteinuria in the overall patient population. However, it significantly suppressed the exacerbation of proteinuria grade in patients with HCC receiving bevacizumab who had diabetes and sBP ≥ 130 mmHg.