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The effect of dapagliflozin on renal function in patients with type 2 diabetes

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Abstract

Background

Dapagliflozin’s antihyperglycemic effects are mediated by inhibition of renal sodium-glucose cotransporter-2; therefore, renal safety of dapagliflozin was assessed.

Methods

Twelve double-blind, placebo-controlled, randomized clinical trials were analyzed up to 24 weeks (N = 4545). Six of the 12 studies included long-term data for up to 102 weeks (N = 3036). Patients with type 2 diabetes with normal or mildly impaired renal function [estimated glomerular filtration rate (eGFR) 60 to <90 mL/min/1.73 m2] were treated with dapagliflozin (2.5, 5, or 10 mg/day) or placebo. Renal adverse events (AEs) were assessed.

Results

Mean eGFR showed small transient reductions with dapagliflozin at week 1, but returned to near baseline values by week 24 and remained stable to week 102. Mean eGFR changes were not very different for dapagliflozin 2.5, 5 and 10 mg versus placebo at 102 weeks: −0.74, 2.52 and 1.38 versus 1.31 mL/min/1.73 m2, respectively. Renal AEs were similar in frequency to placebo through 24 weeks (1.4, 1.3, 0.9, and 0.9 %, respectively) and 102 weeks (2.4, 1.8, 1.9 and 1.7 %, respectively). Few were serious (0.2, 0.1, 0 and 0.3 %, respectively, over 102 weeks). The most common renal event was serum creatinine increase. In sub-group analyses in patients ≥65 years of age or those with moderate renal impairment (eGFR 30 to <60 mL/min/1.73 m2), renal AEs occurred more frequently with dapagliflozin than placebo. No events of acute tubular necrosis were reported.

Conclusion

In patients with normal or mildly impaired renal function, dapagliflozin is not associated with increased risk of acute renal toxicity or deterioration of renal function. All trials included in this analysis are registered at ClinicalTrials.gov: NCT00263276, NCT00972244, NCT00528372, NCT00736879, NCT00528879, NCT00855166, NCT00357370, NCT00680745, NCT00683878, NCT00673231, NCT00643851, NCT00859898.

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Acknowledgments

The study team would like to acknowledge the patients for their participation and commitment during the studies. We also thank the investigators and contributors from each study site. The authors thank Dr. Bruce Leslie for his involvement with this analysis, Dr James List for his contribution to the analysis and initial manuscript development, and Jennifer Sugg for her contribution to statistical analysis. Professional medical writing and editorial assistance was provided by Carolyn Carroll, PhD, an employee of Bristol-Myers Squibb at the time of the development of this manuscript and Shelley Narula, MBBS, of inScience Communications, Springer Healthcare.

Funding

The conduct and analyses of these trials were supported by Bristol-Myers Squibb and AstraZeneca.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA

    Donald Elliott Kohan

  2. Department of Medicine, University of Padua, Padua, Italy

    Paola Fioretto

  3. Global Medical Affairs, AstraZeneca, Mölndal, Sweden

    Kristina Johnsson

  4. Global Medical Affairs, AstraZeneca, Wilmington, DE, USA

    Shamik Parikh

  5. Bristol-Myers Squibb, Research and Development, Route 206 and Provinceline Road, Princeton, NJ, 08543, USA

    Agata Ptaszynska & Lisa Ying

Authors
  1. Donald Elliott Kohan
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  2. Paola Fioretto
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  5. Agata Ptaszynska
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Corresponding author

Correspondence to Agata Ptaszynska.

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Conflict of interest

DEK is a consultant for Bristol-Myers Squibb and AstraZeneca. PF is a consultant for Bristol-Myers Squibb and AstraZeneca, and participant in boards for Boehringer Ingelheim. KJ and SP are employees and shareholders of AstraZeneca. AP and LY are employees and shareholders of Bristol-Myers Squibb.

Ethical approval

The analysis in this article is based on previously conducted studies, and does not involve any new studies of human or animal subjects performed by any of the authors.

Informed consent

Informed consent was obtained from all participants.

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Kohan, D.E., Fioretto, P., Johnsson, K. et al. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol 29, 391–400 (2016). https://doi.org/10.1007/s40620-016-0261-1

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  • DOI: https://doi.org/10.1007/s40620-016-0261-1

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