Clinical Study
Empagliflozin Increases Short-Term Urinary Volume Output in Artificially Induced Syndrome of Inappropriate Antidiuresis
Table 1
Clinical and laboratory variables shown as mean (standard deviation) according to the different timepoints.
| | −1 | 0 | 2 | 8 | Treatment effect | | | Empagliflozin | Placebo | Empagliflozin | Placebo | Empagliflozin | Placebo | Empagliflozin | Placebo | Empagliflozin versus placebo |
| | Clinical evaluations | | | | | | | | | | | | Blood pressure (mmHg) | 122/76 (13/9) | 125/78 (14/8) | 125/82(17/8) | 129/85 (14/9) | 124/75 (13/7) | 124/76 (14/8) | 127/71 (16/9) | 126/75 (16/8) | — | | | Pulse (bpm) | 62 (10) | 64 (10) | 58 (9) | 57 (10) | 58 (8) | 59 (10) | 61 (8) | 60 (9) | — | | | Weight (kg) | 75.6 (14) | 75.7 (13.1) | 77.5 (14.1) | 77.6 (13.4) | 77.6 (14.1) | 77.9 (13.4) | 77 (13.9) | 77.3 (13.2) | 0.08 (−0.18, 0.33) | 0.556 | | Urinary volume excretion (ml) | — | — | 202 (98) | 229 (142) | 165 (69) | 140 (88.5) | 579 (195) | 367 (159) | 158 (48.29, 267.74) | 0.017 | | Laboratory values | | | | | | | | | | | | Serum | | | | | | | | | | | | Sodium (mmol/l) | 140 (1.5) | 140 (1.3) | 136 (2.1) | 137 (2.1) | 133 (1.6) | 133 (2.3) | 132 (1.5) | 132 (2) | 0.2 (−7.38, 6.98) | 0.960 | | Osmolality (mmol/kg) | 286 (2.9) | 286 (4.7) | 278 (4) | 281 (6.7) | 269 (3.3) | 269 (4) | 270 (6.2) | 267 (3.5) | −0.61 (−3.91, 2.68) | 0.721 | | Glucose (mmol/l) | 4.8 (0.4) | 5.1 (0.5) | 4.7 (0.3) | 4.7 (0.4) | 4.5 (0.3) | 4.8 (0.2) | 4.1 (0.5) | 4.5 (0.3) | −0.16 (−0.48, 0.17) | 0.367 | | Urine | | | | | | | | | | | | Sodium (mmol/l) | 108 (38) | 106 (41) | 51 (30) | 50 (36) | 80 (39) | 86 (41) | 188 (27) | 237 (59) | — | | | Total natriuresis (mmol) | — | — | — | — | 14.1 (9.7) | 12.9 (12.4) | 83.3 (42) | 64.4 (41) | 8.54 (−14.19, 31.27) | 0.498 | | Osmolality (mmol/kg) | 678 (249) | 586 (240) | 302 (175) | 260 (178) | 536 (121) | 468 (151) | 823 (60) | 879 (98) | −48.75 (−116.78, 19.28) | 0.185 | | Glucose (mmol/l) | 0.3 (0.2) | 0.3 (0.1) | 0.1 (0.1) | 0.1 (0.1) | 67.5 (46.7) | 0.2 (0.1) | 174.8 (42.1) | 0.4 (0.1) | — | | | Total glucosuria (mmol) | — | — | — | — | 9.5 (5.6) | 0.0 (0.0) | 74.18 (22.3) | 0.12 (0.04) | 2.85 (2.75, 2.96) | <0.001 | | Fractional excretion | | | | | | | | | | | | FE urea (%) | 44.6 (6.2) | 44.3 (8.3) | 49.9 (5.3) | 50.4 (6.9) | 40.8 (7.6) | 32.2 (8.5) | 42.9 (5.3) | 30.6 (9.0) | 8.49 (2.56, 14.41) | 0.016 | | FE uric acid (%) | 5.8 (1.4) | 5.2 (2.2) | 6.4 (1.7) | 6.2 (1.9) | 10.2 (1.9) | 8.6 (2.4) | 10.9 (2.9) | 6.4 (1.7) | 3.93 (1.01, 6.86) | 0.022 | | Biomarkers | | | | | | | | | | | | Copeptin (pmol/l) | 5.9 (3.7) | 5 (1.9) | — | — | 3.1 (0.7) | 3.1 (0.7) | 3.3 (1.8) | 2.6 (0.5) | 0.36 (−1.09, 1.82) | 0.63 | | NT-proBNP (ng/l) | 27.1 (14.0) | 31.7 (18.6) | — | — | 30.3 (17.4) | 34.4 (21.5) | 50.9 (32.2) | 50.5 (33.0) | 4.94 (−13.00, 22.87) | 0.59 | | MR-proANP (pmol/l) | 48.7 (11.8) | 49.2 (16.7) | — | — | 61.7 (14.8) | 59.3 (15.1) | 63.1 (18.9) | 56.8 (8.9) | 6.92 (−5.94, 19.77) | 0.31 | | Aldosterone (pmol/l) | 371.2 (253.1) | 314.7 (154.1) | — | — | 175.6 (93.3) | 154.1 (59.0) | 128.5 (60.1) | 86.7 (23.6) | 29.73 (−14.53, 73.99) | 0.21 | | Renin (ng/l) | 14.3 (9.4) | 21.2 (26.7) | — | — | 6.3 (5.3) | 8.4 (7.4) | 4.9 (5.1) | 3.6 (3.2) | 1.93 (−1.55, 5.40) | 0.29 |
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Timepoint 8 = cumulative excretion during observation period; AUC sodium observation period; values on log scale; FE: fractional excretion. Treatment effect: estimated effect sizes (95% confidence interval) empagliflozin versus placebo, values according to mixed effects models.
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