The systemic and kidney hemodynamic response to empagliflozin, losartan and their combination varies between individuals

Background: Renin-angiotensin system inhibitors (RASi) and sodium glucose cotransporter inhibitors (SGLT2i) are known for their kidney protective properties, but both show significant residual risk in large outcome trials. In these trials, SGLT2i were introduced on top of RASi; the individual response to each drug is currently unclear. We therefore aimed to investigate the individual reactions to the angiotensin II receptor blocker (ARB) losartan and the SGLT2i empagliflozin and their combination on measured GFR (mGFR) and systolic blood pressure (SBP). Methods: In this double-blind, randomized, 4-armed, crossover study, 24 participants received 7 days of empagliflozin 10 mg once daily, losartan 50 mg once daily, combination therapy or matching placebo. We visualized individual drug response variability. We further explored predictors of mGFR and SBP changes. Results: During empagliflozin administration, a greater than 10% reduction in mGFR was observed in 26% of participants receiving empagliflozin, in 30% of those receiving losartan, and in 39% among participants on combination therapy. In comparison, a greater than 10% reduction in SBP was observed in 35% of participants on empagliflozin, in 39% of those receiving losartan and in 43% on combination therapy. A large part of the participants who did not respond to one drug, did respond to the other drug or their combination. Monotherapy SGLT2i did not correlate with monotherapy ARB in mGFR change or SBP change. Conclusions: Our data show large individual variability in response to treatment with the ARB losartan and the SGLT2i empagliflozin. Clinicians should monitor treatment responses in patients and consider switching from one kidney protective drug to another in non-responders.