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Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers
Authors:Hiddo J. L. Heerspink PhD  C. David Sjöström MD  Silvio E. Inzucchi MD  Melissa K. Hallow PhD  Valerie A. Cain MS  Peter Rossing MD  Bergur V. Stefansson PhD  Peter Sartipy PhD
Affiliation:1. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center, Groningen, The Netherlands;2. AstraZeneca, Gothenburg, Sweden;3. Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut;4. Department of Epidemiology and Biostatistics, University of Georgia School of Public Health, Athens, Georgia;5. Bogier Clinical and IT Solutions, Inc., Raleigh, North Carolina;6. Steno Diabetes Center Copenhagen, Gentofte, Denmark

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;7. AstraZeneca, Gothenburg, Sweden

Systems Biology Research Center, School of Bioscience, University of Skövde, Skövde, Sweden

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
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