SAT-300 EFFECTS OF DAPAGLIFLOZIN AND DAPAGLIFLOZIN PLUS SAXAGLIPTIN ON HbA1c AND ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE: PHASE II/III DELIGHT STUDY

Introduction: Suboptimal glycemic control is often associated with albuminuria and decline in estimated GFR (eGFR) in patients with diabetic kidney disease (DKD). Sodium-glucose linked transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have individually been shown to exert benefit on glycemic control and/or albuminuria in patients with DKD. We assessed the effects of the SGLT2 inhibitor dapagliflozin (dapa) alone and in combination with the DPP4 inhibitor saxagliptin (saxa) on albuminuria and HbA1c in patients with Type 2 diabetes and DKD. Methods: The trial enrolled patients from nine countries (Australia, Canada, Japan, Republic of Korea, Mexico, South Africa, Spain, Taiwan, and the United States of America). Inclusion criteria comprised urinary albumin-to-creatinine ratio (UACR) 30–3500 mg/g, eGFR 25–75 mL/min/1.73 m2, HbA1c 7–11%, and stable doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and glucose lowering treatment for ≥12 weeks. After a 4-week single blind placebo run-in period, 448 eligible patients were randomized (1:1:1) to dapa 10 mg, dapa 10 mg/saxa 2.5 mg combination or placebo once daily for 24 weeks. Type I error control allowed for separate comparisons between dapa/saxa or dapa with placebo; separate hierarchical test procedures were used for inference. The primary endpoint for dapa was percent change in UACR from baseline to Week 24; co-primary endpoints for dapa/saxa were percent change in UACR from baseline and change from baseline in HbA1c. Primary comparisons with placebo corresponded to Week 24 differences in least square mean estimates obtained from mixed models for repeated measures. Safety was assessed throughout (adverse events [AEs] and laboratory data). Results: Both dapa alone and dapa/saxa significantly reduced UACR compared to placebo. This effect was sustained over the study period; at Week 24, change in UACR versus placebo was −21.0 (−34.1, −5.2; p=0.011) and −38.0% (−48.2, −25.8; p<0.001) for the two arms, respectively. Dapa/saxa also significantly reduced HbA1c compared to placebo: at Week 24, change in HbA1c was −0.58% (−0.80, −0.37); p<0.001. Dapa and dapa/saxa were well-tolerated and no new drug-related safety signals were observed. AEs occurred in 79 (54.5%), 104 (68.4%) and 81 (54.7%) patients in the dapa, dapa/saxa and placebo arms, respectively, and serious AEs in 12 (8.3%), 12 (7.9%) and 16 (10.8%) patients; 4 (2.8%), 7 (4.6%) and 8 (5.4%) patients discontinued due to AEs. Two deaths occurred, one in each treatment group. Conclusions: Both dapa and dapa/saxa conferred significant improvements in albuminuria, with dapa/saxa additionally conferring a clinically significant reduction in HbA1c at Week 24 in patients with DKD. The DELIGHT study (clinicaltrials.gov NCT02547935) was sponsored by AstraZeneca.