Abstract: SA-PO137
Effects of the SGLT-2 Inhibitor Dapagliflozin on Volume Status in Patients with Type 2 Diabetes and Elevated Albuminuria
Session Information
- Diabetic Kidney Disease: Clinical - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Dekkers, Claire, University Medical Center Groningen, Groningen, Netherlands
- Gansevoort, Ron T., University Medical Center Groningen, Groningen, Netherlands
- Kramers, Bart J., Harvard, Groningen, Netherlands
- Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
Background
SGLT-2 inhibitors reduce the risk for heart failure events in patients with type 2 diabetes at high cardiovascular risk. These beneficial effects are thought to be attributed to diuretic effects. The aim of this study was to assess whether these diuretic effects can be attributed to osmotic or natriuretic diuresis in patients with type 2 diabetes and elevated albuminuria.
Methods
A post-hoc analysis was performed of a randomized placebo controlled cross-over trial that assessed the effects of dapagliflozin (DAPA) 10 mg/day therapy in 31 patients with type 2 diabetes and elevated albuminuria (median UAE 521 mg/24h). Blood samples and 24-hour urine were collected at start and end of each 6-weeks treatment period. Markers of volume status including sodium, urea, copeptin, renin, NT-proBNP and osmolality were measured. Free water clearance (FWC) was calculated as urine flow minus osmolar clearance.
Results
Compared to placebo, DAPA therapy increased fractional lithium excretion (reflecting reduced sodium reabsorption), urinary glucose excretion, urine osmolality, copeptin and renin, and it decreased FWC (table). DAPA therapy did not change plasma osmolality, sodium, and NT-proBNP.
Conclusion
The observed increases in fractional lithium excretion, glucose excretion and urine osmolality, and the combined increase in copeptin and renin during DAPA therapy suggests that both osmotic and natriuretic diuresis are involved. These findings are based on 6-weeks changes in fluid markers, when patients already have reached a new steady state. Further research is needed to characterize acute volume and diuretic effects of DAPA.
| Volume biomarkers | DAPA Mean (95% CI) | PLACEBO Mean (95% CI) | Effect of DAPA vs PLACEBO Mean (95% CI) | P-value |
| Urea (mmol/l) | 1.2 (0.6 to 1.8) | 0.1 (-0.5 to 0.7) | 1.1 (0.3 to 1.9) | <0.01 |
| Sodium (mmol/l) | 0.3 (-0.4 to 1.1) | -0.1 (-0.8 to 0.7) | 0.4 (-0.4 to 1.2) | 0.35 |
| Plasma osmolality (mosmol/kg) | -0.2 (-2.0 to 1.5) | -1.0 (-2.7 to 0.7) | 0.8 (-1.1 to 2.7) | 0.40 |
| Copeptin (pmol/l) | 3.4 (2.1 to 4.8) | -0.3 (-1.7 to 1.0) | 3.8 (2.1 to 5.5) | <0.01 |
| Renin (%) | 71.6 (33.0 to 121.4) | 14.2 (-10.7 to 45.9) | 50.3 (7.0 to 111.2) | 0.02 |
| NT-proBNP (%) | -3.6 (-19.6 to 15.5) | -10.6 (-24.9 to 6.4) | 7.8 (-16.2 to 38.7) | 0.55 |
| Urine osmolality (mOsmol/kg) | 34.3 (-8.5 to 77.2) | -27.5 (-67.5 to 12.4) | 61.8 (12.2 to 111.5) | 0.02 |
| Fractional lithium excretion (%) | 24.3 (10.1 to 40.3) | 2.7 (-8.6 to 15.5) | 21.0 (4.9 to 39.6) | 0.01 |
| Urinary glucose excretion (mmol/24h) | 217.5 (176.0 to 259.0) | 7.9 (-30.7 to 46.5) | 209.5 (148.7 to 270.4) | <0.01 |
| FWC (ml/24h) | -503.7 (-791.3 to -216.2) | 38.4 (-229.8 to 306.6) | -542.1 (-880.2 to –204.1) | <0.01 |