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

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2019-03, Vol.21 (3), p.720-725
• Main Authors: Heerspink, Hiddo J. L., Sjöström, C. David, Inzucchi, Silvio E., Hallow, Melissa K., Cain, Valerie A., Rossing, Peter, Stefansson, Bergur V., Sartipy, Peter
• Format: Article
• Language: English
• Subjects: Aged; Albumins - analysis; albuminuria; Albuminuria - prevention & control; Albuminuria - urine; Antidiabetics; Benzhydryl Compounds - therapeutic use; Bioinformatics; Bioinformatik; Biomarkers - analysis; Biomarkers - blood; Biomarkers - urine; Blood pressure; Body weight; Brief Report; Brief Reports; Cardiovascular diseases; Clinical trials; Clinical Trials, Phase III as Topic - statistics & numerical data; Creatinine; Creatinine - analysis; Creatinine - urine; dapagliflozin; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - urine; Diabetic Angiopathies - blood; Diabetic Angiopathies - physiopathology; Diabetic Angiopathies - prevention & control; Diabetic Angiopathies - urine; Diabetic Nephropathies - blood; Diabetic Nephropathies - physiopathology; Diabetic Nephropathies - prevention & control; Diabetic Nephropathies - urine; Down-Regulation - drug effects; Female; Glomerular filtration rate; Glomerular Filtration Rate - drug effects; Glucose transporter; Glucosides - therapeutic use; Humans; Hypertension; Hypertension - complications; Hypertension - drug therapy; INF502 Biomarkers; INF502 Biomarkörer; Male; Middle Aged; Patients; Randomized Controlled Trials as Topic - statistics & numerical data; Retrospective Studies; Risk Factors; Sodium; sodium glucose co-transporter-2
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.13579

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.