{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:33:11Z","timestamp":1793118791499,"version":"4.5.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,11,3]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>SGLT2 (sodium-glucose cotransporter-2) inhibitors improve heart failure\u2013associated outcomes in patients with type 2 diabetes. In patients with heart failure, SGLT2 inhibitors will likely be coprescribed with a loop diuretic, but this combined effect is not well-defined. Our aim was to assess the diuretic and natriuretic effect of empagliflozin in combination with loop diuretics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>The RECEDE-CHF trial (SGLT2 Inhibition in Combination With Diuretics in Heart Failure) was a randomized, double-blind, placebo-controlled, crossover trial of patients with type 2 diabetes and heart failure with reduced ejection fraction taking regular loop diuretic who were randomized to empagliflozin 25 mg once daily or placebo for 6 weeks with a 2-week washout period. The primary outcome was change in 24-hour urinary volume from baseline to week 6.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Twenty-three participants (mean age, 69.8 years; 73.9% male; mean furosemide dose, 49.6\u00b131.3 mg\/d; mean HbA1c, 7.9\u00b13.8%) were recruited. Compared with placebo, empagliflozin caused a significant increase in 24-hour urinary volume at both day 3 (mean difference, 535 mL [95% CI, 133\u2013936];\n              <jats:italic>P<\/jats:italic>\n              =0.005) and week 6 (mean difference, 545 mL [95% CI, 136\u2013954];\n              <jats:italic>P<\/jats:italic>\n              =0.005) after adjustment for treatment order, baseline 24-hour urine volume, and percentage change in loop diuretic dose. At 6 weeks, empagliflozin did not cause a significant change in 24-hour urinary sodium (mean difference, \u22127.85 mmol\/L [95% CI, \u22122.43 to 6.73];\n              <jats:italic>P<\/jats:italic>\n              =0.57). Empagliflozin caused a nonsignificant increase in fractional excretion of sodium at day 3, which was absent at week 6 (mean difference day 3, 0.30% [95% CI, \u22120.03 to 0.63];\n              <jats:italic>P<\/jats:italic>\n              =0.09; week 6, 0.11% [95% CI, \u22120.22 to 0.44];\n              <jats:italic>P<\/jats:italic>\n              &gt;0.99), and a significant increase in electrolyte-free water clearance at week 6 (mean difference, 312 mL [95% CI, 26\u2013598];\n              <jats:italic>P<\/jats:italic>\n              =0.026) compared with placebo. Empagliflozin also caused significant reductions in body weight and serum urate at week 6.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Empagliflozin caused a significant increase in 24-hour urine volume without an increase in urinary sodium when used in combination with loop diuretic.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique Identifier: NCT03226457.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.120.048739","type":"journal-article","created":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T06:30:11Z","timestamp":1598769011000},"page":"1713-1724","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":228,"title":["Renal and Cardiovascular Effects of SGLT2 Inhibition in Combination With Loop Diuretics in Patients With Type 2 Diabetes and Chronic Heart Failure"],"prefix":"10.1161","volume":"142","clinical-trial-number":[{"clinical-trial-number":"nct03226457","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Natalie A.","family":"Mordi","sequence":"first","affiliation":[{"name":"Division of Molecular and Clinical Medicine, University of Dundee, Scotland, United Kingdom (N.A.M., I.R.M., R.J.M., A.D.S., C.C.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ify R.","family":"Mordi","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, University of Dundee, Scotland, United Kingdom (N.A.M., I.R.M., R.J.M., A.D.S., C.C.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7358-9712","authenticated-orcid":true,"given":"Jagdeep S.","family":"Singh","sequence":"additional","affiliation":[{"name":"Royal Infirmary of Edinburgh, Scotland, United Kingdom (J.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3957-1981","authenticated-orcid":true,"given":"Rory J.","family":"McCrimmon","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, University of Dundee, Scotland, United Kingdom (N.A.M., I.R.M., R.J.M., A.D.S., C.C.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan D.","family":"Struthers","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, University of Dundee, Scotland, United Kingdom (N.A.M., I.R.M., R.J.M., A.D.S., C.C.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4530-3078","authenticated-orcid":true,"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, University of Dundee, Scotland, United Kingdom (N.A.M., I.R.M., R.J.M., A.D.S., C.C.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2015.10.012"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2017.1891"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.030012"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-3956-x"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4670-7"},{"key":"e_1_3_5_11_2","unstructured":"Richards M. 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