Op-ndtj170430 1..7

Background. The sodium–glucose co-transporter 2 inhibitor dapagliflozin decreases haemoglobin A1c (HbA1c), body weight, blood pressure (BP) and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes. The efficacy and safety of this drug have not been properly defined in patients with type 2 diabetes and Stages 3b–4 chronic kidney disease (CKD). Methods. In a pooled analysis of 11 phase 3 randomized controlled clinical trials, we determined least square mean changes in HbA1c, body weight, BP, estimated glomerular filtration rate (eGFR) and UACR over 102weeks in patients with type 2 diabetes and an eGFR between 12 to less than 45mL/min/1.73 m receiving placebo (n1⁄4 69) or dapagliflozin 5 or 10mg (n1⁄4 151). Effects on UACR were determined in a subgroup of patients with baseline UACR 30mg/g (n1⁄4 136). Results. Placebo-corrected changes in HbA1c with dapagliflozin 5 and 10mg were 0.03% [95% confidence interval (CI) 0.3–0.3] and 0.03% (95% CI 0.2–0.3) during the overall 102week period. Dapagliflozin 5 and 10mg compared with placebo reduced UACR by 47.1% (95% CI 64.8 to 20.6) and 38.4% (95% CI 57.6 to 10.3), respectively. Additionally, dapagliflozin 5 and 10mg compared with placebo reduced BP and body weight. eGFR increased with placebo during the first 4weeks but did not change with dapagliflozin. There were no between-group differences in eGFR at the end of follow-up. Adverse events associated with renal function occurred more frequently in the dapagliflozin 10-mg group. These events were mainly asymptomatic increases in serum creatinine. Conclusions. Dapagliflozin did not decrease HbA1c in patients with type 2 diabetes and Stages 3b–4 CKD, but decreased UACR, BP and body weight to a clinically meaningful extent. These results support a large outcome trial in this population to confirm longterm safety and efficacy in reducing adverse clinical endpoints.