400-P: More Pronounced Effect of Empagliflozin-Losartan Combination Therapy on Measured GFR and Blood Pressure vs. Either of the Drugs: A Crossover RCT in People with Type 2 Diabetes
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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