Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and renin-angiotensin system inhibitors (RASi) improve kidney outcomes in people with type 2 diabetes (T2D) . Both drugs favorably affect kidney hemodynamic function which is characterized an acute GFR drop (reflecting reduced glomerular pressure) which, in part, underlies their protective effects. However, the interaction of these drugs on systemic and kidney hemodynamics is unstudied.

Methods: During this 4-arm, cross-over, placebo-controlled, double-blind intervention trial, twenty-four T2D patients on metformin and/or sulfonylurea therapy, (age 66±6 years, HbA1c 7.4±0.9%, measured GFR 108±20 mL/min, hypertension treated by beta blockers) were randomized to one-week treatment with empagliflozin (EMPA) 10mg QD, losartan (LOS) 50mg QD, empagliflozin+losartan (EMPA+LOS) and placebo. Fasting GFR was measured by steady-state plasma iohexol clearances. Blood pressure and heart rate (HR) were recorded. Statistical comparisons were done by Friedman test and Wilcoxon rank test correcting for multipele comparisons.

Results: Versus placebo, EMPA and LOS monotherapy reduced GFR by 7.0 mL/min (p=0.003) and 7.3 mL/min (p=0.01) respectively, while EMPA+LOS reduced by GFR by 10.7 mL/min (p<0.001) . Versus placebo, all treatment lowered blood pressure: EMPA -8.7 mmHg (p=0.04) , LOS -12.4 mmHg (p=<0.001) and EMPA+LOS -15.1 mmHg (p<0.001) . HR was unchanged. No safety concerns were observed.

Conclusion: In people with T2D and preserved kidney function, empagliflozin-losartan therapy induces more pronounced effects on measured GFR and blood pressure versus either of the drugs. These data support their combined use to improve kidney outcomes.


D.Van raalte: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi. H.L.Heerspink: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., Goldfinch Bio, Inc., Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Mundipharma, Traveere Pharmaceuticals, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. R.Scholtes: None.

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