{"id":"4cf984eddf35","type":"article","url":"https://hartvaat.nl/2024/04/16/sglt2-remming-waterconservatie-domineert-over-osmotische-diurese-bij-hf/","title":"SGLT2-remming: waterconservatie domineert over osmotische diurese bij HF","title_en":"Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure.","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog","internist"],"tags":[],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2024.02.020","source_url":"https://doi.org/10.1016/j.jacc.2024.02.020","authors":["Adriana Marton","Seyed Ehsan Saffari","Manfred Rauh","Ruo-Ning Sun","Armin M Nagel","Peter Linz","Tzy Tiing Lim","Kaoru Takase-Minegishi","Anastacia Pajarillaga","Sharon Saw","Norihiko Morisawa","Wan Keat Yam","Shintaro Minegishi","John J Totman","Serena Teo","Louis L Y Teo","Choon Ta Ng","Kento Kitada","Johannes Wild","Jean-Paul Kovalik","Friedrich C Luft","Peter J Greasley","Calvin W L Chin","David K L Sim","Jens Titze"],"significance":6,"published":"2024-04-16","source_date":"2024-04-16","image":"","kennis":["https://hartvaat.nl/kennis/hartfalen/sglt2-remmers-bij-hartfalen/","https://hartvaat.nl/kennis/hartfalen/esc-richtlijn-hartfalen-2021/"],"congress":"","summary_en":"This mechanistic study showed that the osmotic diuretic potential of SGLT2 inhibitors in heart failure is attenuated by compensatory renal water conservation, suggesting that the cardiac benefit operates through mechanisms beyond volume reduction.","created":"2026-07-03T10:30:52Z","updated":"2026-07-03T13:29:55Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Mechanistische studie toonde dat de diuretische werking van SGLT2-remmers bij hartfalen beperkt wordt door renale waterconservatie. De klinische voordelen verlopen waarschijnlijk via andere mechanismen dan directe diurese.","abstract_original":"BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. RESULTS: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70). CONCLUSIONS: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518)."}