Key result
SGLT2 inhibitors fail to delay proteinuria exacerbation in HCC patients on atezolizumab plus bevacizumab.
Why the study?
SGLT2 inhibitors reduce proteinuria in diabetes and chronic kidney disease, but their effect on vascular endothelial growth factor inhibitor-induced proteinuria remains unclear.
Do SGLT2 inhibitors prevent exacerbation of proteinuria in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab?
Cohort (n=188)
Yes
Do SGLT2 inhibitors prevent exacerbation of proteinuria in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab?
Absolute Event Rate: 157% vs 116%
p-value: p=0.95
SGLT2 inhibitors do not prevent bevacizumab-induced proteinuria in the overall HCC population, but may delay progression in high-risk patients with concurrent diabetes and hypertension.
SGLT2 inhibitors should not yet change practice for bevacizumab proteinuria in HCC; leaves open subgroup effects in diabetes with hypertension.
Background/Aim: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce proteinuria in patients with diabetes mellitus and chronic kidney disease. However, their effect on vascular endothelial growth factor inhibitor-induced proteinuria remains unclear. This study evaluated the prophylactic effect of SGLT2i on bevacizumab-induced proteinuria in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab. Patients and Methods: This multicenter retrospective study included patients with HCC who started therapy with atezolizumab plus bevacizumab between September 2020 and December 2023. The primary outcome was the time to exacerbation of proteinuria from baseline within 6 months after treatment initiation according to SGLT2i use. Secondary outcomes included the development of grade ≥2 proteinuria. Results: A total of 188 patients were included, of whom 29 received SGLT2i. No significant difference in the time to exacerbation of proteinuria was observed between the SGLT2i and non-SGLT2i groups considering the overall population (median: 157 vs. 116 days, p=0.95). Multivariate analysis identified diabetes with systolic blood pressure ≥130 mmHg as an independent risk factor for proteinuria exacerbation (hazard ratio=2.19, 95% confidence interval=1.18-4.06, p=0.013), whereas SGLT2i use was not significantly associated with proteinuria exacerbation. In patients with both diabetes and systolic blood pressure ≥130 mmHg, SGLT2i significantly prolonged the time to proteinuria exacerbation. Conclusion: SGLT2i may suppress proteinuria progression only in high-risk patients with HCC complicated by diabetes and hypertension.
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Hori et al. (2026) conducted a cohort in Hepatocellular carcinoma (HCC) (n=188). SGLT2 inhibitors vs. non-SGLT2i was evaluated on Time to exacerbation of proteinuria from baseline within 6 months after treatment initiation (p=0.95). SGLT2 inhibitor use did not significantly prolong the time to proteinuria exacerbation compared to non-use in patients with HCC receiving atezolizumab plus bevacizumab (median 157 vs 116 days; p=0.95).
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