Kidney Week

Abstract: FR-PO238

Effects of the SGLT2 Inhibitor Dapagliflozin on Plasma Volume in Patients with Type 2 Diabetes and Various eGFR Levels

Session Information

• Diabetic Kidney Disease: Advancing Treatment
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington 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

Claire Dekkers,

• Sjostrom, David, AstraZeneca LP, Molndal, Sweden

David Sjostrom,

• Greasley, Peter J., AstraZeneca, Mölndal, Sweden

Peter J. Greasley,

• Cain, Valerie, Bogier Clinical and IT Solutions, Inc, Haddonfield, New Jersey, United States

Valerie Cain,

• Boulton, David W., AstraZeneca, Mölndal, Sweden

David W. Boulton,

• L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink,

Background

Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the rate of renal outcomes and heart failure events in patients with type 2 diabetes and chronic kidney disease possibly as a result of volume contraction. In this study we compare the effects of dapagliflozin on estimated and measured plasma volume and we investigate whether kidney function and other relevant characteristics modify effects of dapagliflozin on estimated plasma volume.

Methods

The Strauss formula was used to calculate changes in estimated plasma volume (ePV). Change in plasma volume measured with ¹²⁵I-human serum albumin (mPV) was compared with change in ePV in a study of patients with type 2 diabetes randomized to dapagliflozin 10 mg/day or placebo. Subsequently, changes in ePV were measured in a pooled database of 13 phase 2b/3 placebo controlled clinical trials involving 4533 patients with type 2 diabetes randomized to dapagliflozin 10 mg/day or placebo.

Results

Median change in ePV was similar to median change in mPV (-9.4 and -9.0 %) during dapagliflozin treatment. In the pooled analysis, dapagliflozin compared to placebo decreased ePV by 9.6 % (95% CI: 9.0 to 10.2%) after 24 weeks. This effect was consistent in various eGFR-groups (ePV changes of -9.5, -9.7 and -9.5 in eGFR subgroups <60, 60-90, and ≥90 ml/min/1.73m² [Figure 1]).

Conclusion

Dapagliflozin consistently decreased estimated plasma volume compared to placebo in a broad population of patients with type 2 diabetes underpinning heart failure benefits observed in patients with type 2 diabetes and chronic kidney disease.

Figure 1: Changes from baseline in estimated plasma volume (%) during 24 week treatment with dapagliflozin relative to placebo in various subgroups