Effects of the sodium-glucose co-Transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease

Abstract

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 102 weeks in patients with type 2 diabetes and an EGFR between 12 to less than 45 mL/min/1.73 m 2 receiving placebo (n = 69) or dapagliflozin 5 or 10 mg (n = 151). Effects on UACR were determined in a subgroup of patients with baseline UACR ≥30 mg/g (n = 136). Results Placebo-corrected changes in HbA1c with dapagliflozin 5 and 10 mg were 0.03% [95% confidence interval (CI) â '0.3-0.3] and 0.03% (95% CI â '0.2-0.3) during the overall 102-week period. Dapagliflozin 5 and 10 mg compared with placebo reduced UACR by â ' 47.1% (95% CI â '64.8 to â ' 20.6) and â '38.4% (95% CI â '57.6 to â ' 10.3), respectively. Additionally, dapagliflozin 5 and 10 mg compared with placebo reduced BP and body weight. EGFR increased with placebo during the first 4 weeks 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 long-Term safety and efficacy in reducing adverse clinical endpoints.