Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Mar;21(3):720-725.
doi: 10.1111/dom.13579. Epub 2018 Dec 11.

Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers

Hiddo J L Heerspink  1 , C David Sjöström  2 , Silvio E Inzucchi  3 , Melissa K Hallow  4 , Valerie A Cain  5 , Peter Rossing  6   7 , Bergur V Stefansson  2 , Peter Sartipy  2   8
Affiliations

Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers

Hiddo J L Heerspink et al. Diabetes Obes Metab. 2019 Mar.

Abstract

The sodium glucose co-transporter-2 inhibitor dapagliflozin has been shown to decrease urinary albumin-to-creatinine ratio (UACR). This effect, however, varies among individual patients. In this study, we assessed the baseline characteristics and concurrent changes in other cardiovascular risk markers that might be associated with UACR response to dapagliflozin. A pooled analysis of 11 phase 3 randomized, controlled clinical trials was performed. UACR change from baseline after 24 weeks treatment with dapagliflozin 10 mg/d in 531 patients with type 2 diabetes and UACR ≥30 mg/g at baseline was determined. UACR response was defined as >30% reduction from baseline at 24 weeks, whereas UACR non-response was defined as ≤30% reduction at 24 weeks. A total of 288 (54%) patients were classified as responders and 243 (46%) as non-responders. At 24 weeks, the UACR-adjusted mean change from baseline was -71.2% and 25.9% in responders and non-responders, respectively. Baseline characteristics were similar between both groups. Changes in HbA1c and body weight were comparable across groups. Responders showed a numerically larger reduction in estimated glomerular filtration rate and systolic blood pressure versus non-responders. UACR reduction to dapagliflozin is an individual characteristic that cannot be predicted by baseline clinical features or changes in metabolic variables. Whether UACR response would improve long-term renal and cardiovascular outcomes remains to be determined.

Keywords: albuminuria; dapagliflozin; diabetes; hypertension; sodium glucose co-transporter-2.

PubMed Disclaimer

Conflict of interest statement

Author contributions

P.S., C.D.S., and B.V.S. designed the study. H.J.L.H. and P.S. wrote the first draft of this manuscript. V.C. performed all statistical analyses. All authors contributed to interpretation and critical revisions of the manuscript. All authors approved the submission for publication. H.J.L.H. and P.S. take full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

Figures

Figure 1
Figure 1
Distribution of albuminuria changes from baseline at week 24. A, Histogram and B, cumulative distribution of UACR changes at week 24; 54.2% of patients experienced >30% reduction in UACR and 71.4% of patients experienced >0% reduction in UACR. Abbreviation: UACR, urine albumin : creatinine ratio
Figure 2
Figure 2
Changes in renal and cardiovascular risk markers over time in UACR responders and non‐responders. A, UACR; B, HbA1c; C, SBP; D, eGFR; E, body weight; F, haematocrit; G, bicarbonate levels; H, sUA. Abbreviations: Adj., adjusted; eGFR, estimated glomerular filtration rate; non‐RES, non‐responders; RES, responders; SBP, systolic blood pressure; sUA, serum uric acid; UACR, urine albumin : creatinine ratio
See this image and copyright information in PMC

References

    1. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double‐blind, placebo‐controlled trial. Lancet. 2010;375:2223‐2233. - PubMed
    1. Weber M, Mansfield T, Cain V, Iqbal N, Parikh S, Ptaszynska A. Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy: a randomised, double‐blind, placebo‐controlled, phase 3 study. Lancet Diabetes Endocrinol. 2016;4:211‐220. - PubMed
    1. Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323‐334. - PubMed
    1. Petrykiv SI, Laverman GD, de Zeeuw D, Heerspink HJL. The albuminuria‐lowering response to dapagliflozin is variable and reproducible among individual patients. Diabetes Obes Metab. 2017;19:1363‐1370. - PubMed
    1. Heerspink HJ, Johnsson E, Gause‐Nilsson I, Cain VA, Sjostrom CD. Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin‐angiotensin blockers. Diabetes Obes Metab. 2016;18:590‐597. - PMC - PubMed

Publication types

MeSH terms