1830-P: Ertugliflozin Reduces Blood Pressure and EGFR during Both Moderate- and High-Sodium Intake in People with Type 2 Diabetes.

Introduction and Objective: SGLT2i lower BP and improve cardio-kidney outcomes in large trials, although interindividual variability is observed. High dietary sodium intake is known to attenuate the BP-lowering efficacy of antihypertensive drugs. Here, we investigated the BP-lowering effects of the SGLT2i ertugliflozin (ERTU) during moderate dietary salt (MS) vs. high dietary salt (HS) intake and hypothesized that ERTU would induce larger reduction during MS. Methods: This randomized, placebo-controlled, 4-arm crossover trial included 34 participants with T2D. They followed MS (90±18 mmol/day) and HS (250±50 mmol/day) diets, with compliance verified by 24-h urinary sodium excretion after 7-10 days. Compliant participants then received 10 days of ERTU 15 mg once daily or matching placebo (PLB) in random order while continuing the diet. At baseline and the end of each treatment period, 24-h ABPM, 24-h urine and blood samples including creatinine were collected. Primary outcome was the difference in BP-lowering effect of ERTU compared to PLB during MS vs. HS. Participants on RASi or diuretics maintained stable dosages throughout the study. Results: Participants were predominantly male (85%), with baseline SBP of 131 ± 10 mmHg, DBP of 80 ± 7 mmHg, and eGFR of 81 ± 12 ml/min/1.73m2. Baseline 24-h urinary sodium excretion was 132.5 [106.0 - 185.3] mmol. During MS, 24-h sodium excretion was similar for ERTU (90.3 ± 43.6 mmol) and PLB (84.2 ± 34.8 mmol). During MS, ERTU lowered SBP and DBP by 4.2 (SE 1.7) mmHg (3.4%; p = 0.017) and 2.1 (SE 1.1) mmHg (2.7%; p = 0.066) vs PLB, respectively. Similarly, during HS, 24-h sodium excretion was comparable between ERTU (234 ±77.6 mmol) and PLB (215 ± 81.9 mmol); ERTU lowered SBP and DBP vs. PLB by 5.2 (SE 1.8) mmHg (3.8%, p = 0.004) and 2.4 (SE 1.1) mmHg (2.9%, p = 0.039), respectively. ERTU vs. PLB also decreased eGFR during both MS (-1.2ml/min/1.73m2) and HS (-2.3 ml/min/1.73m2). Conclusion: ERTU has similar BP-lowering effects during MS and HS intake, suggesting its antihypertensive effect is independent of sodium intake. Disclosure B. Wever: None. C.L. Birznieks: None. L. Driscoll: None. J. Kendrick: Advisory Panel; Current; Fresenius Medical Care. Research Support; Current; Eli Lilly and Company, Bayer AG, Novo Nordisk. H. Heerspink: Consultant; Current; AstraZeneca, Alnylam Pharmaceuticals, Inc., Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Dimerix, Eli Lilly and Company, Novo Nordisk, Novartis AG, Roche Pharmaceuticals. P. Bjornstad: Consultant; Current; Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk. D. van Raalte: Consultant; Current; AstraZeneca. Research Support; Current; AstraZeneca. Consultant; Current; Boehringer Ingelheim International GmbH. Research Support; Current; Boehringer Ingelheim International GmbH. Consultant; Current; Eli Lilly and Company. Research Support; Current; Eli Lilly and Company. Consultant; Current; Merck & Co., Inc. Research Support; Current; Merck & Co., Inc. Consultant; Current; Novo Nordisk. Research Support; Current; Novo Nordisk.