Association between sodium-glucose cotransporter 2 inhibitor use and proteinuria during bevacizumab therapy in patients with type 2 diabetes mellitus: a retrospective cohort study

Abstract Background Bevacizumab (Bev) often causes proteinuria, a clinically important renal adverse event that may necessitate interruption or discontinuation of Bev. However, no effective or safe strategy has been established to prevent proteinuria during Bev therapy. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduces albuminuria and exerts renoprotective effects in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease; however, their clinical effect on proteinuria during Bev therapy remains unclear. In the present study, we investigated the association between SGLT2i use and proteinuria during Bev therapy in patients with T2DM. Methods We retrospectively analyzed the electronic medical records of 160 patients with T2DM who received Bev-containing therapy at The University of Osaka Hospital to examine the association between SGLT2i use and the development of proteinuria during Bev therapy during the 6 months following Bev initiation. Results The incidence of proteinuria during Bev therapy (grade ≥ 2) and discontinuation of Bev due to proteinuria were significantly lower in patients with SGLT2i than in those without SGLT2i (13% vs. 36%, p = 0.032, 0% vs. 15%, p = 0.046, respectively). Competing-risk analysis showed that a lower cumulative incidence of grade ≥ 2 proteinuria in patients with SGLT2i (Gray’s test, p = 0.043). Multivariable Cox regression analysis showed that concomitant SGLT2i use was significantly associated with a lower risk of developing grade ≥ 2 proteinuria (hazard ratio = 0.237, 95% confidence interval: 0.057–0.659, p = 0.004). In contrast, no significant differences were observed in estimated glomerular filtration rate and blood urea nitrogen slope per month between patients treated with and without SGLT2i ( p = 0.901 and p = 0.474, respectively). Conclusions Concomitant SGLT2i use was associated with a lower incidence of grade ≥ 2 proteinuria during Bev therapy in patients with T2DM.