Effects of Dapagliflozin on Health-Related Quality of Life in Patients with CKD

Key Points In patients with CKD with and without type 2 diabetes, treatment with dapagliflozin slowed the decline in health-related quality of life. The effect was particularly evident on physical health–related quality of life, symptom burden, and the effect of kidney disease. Background Treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin attenuates progression of kidney disease and reduces the risks of heart failure and death in patients with CKD. Data on the effects of dapagliflozin on health-related quality of life (QoL) are limited. Methods Adults with CKD, with and without type 2 diabetes, with eGFR 25–75 ml/min per 1.73 m 2 and urinary albumin-to-creatinine ratio 200–5000 mg/g were randomized to dapagliflozin (10 mg/d) or placebo. We assessed health-related QoL using the Kidney Disease Quality of Life Instrument 36 (KDQOL-36) questionnaire at baseline and at 12, 24, and 36 months. In this prespecified analysis, we determined the overall effects of dapagliflozin versus placebo. Results A total of 4032/4304 (94%) randomized participants (mean age 62 [12] years, 32% female) had information on KDQOL-36 at baseline. Mean scores on the physical health composite (PHC), mental health composite (MHC), and kidney disease symptoms, effects, and burden were similar between randomized groups at baseline. During a median follow-up of 2.3 (interquartile range, 1.9–2.6) years, mean scores were significantly higher in participants randomized to dapagliflozin for PHC (0.71 [95% confidence interval (CI), 0.30 to 1.31]), MHC (0.62 [95% CI, 0.14 to 1.11]), kidney disease symptoms (1.33 [95% CI, 0.57 to 2.10]), kidney disease effects (1.34 [95% CI, 0.43 to 2.26]), and kidney disease burden (1.46 [95% CI, 0.30 to 2.62]). Participants randomized to dapagliflozin were significantly less likely to experience a clinically meaningful (≥10 units) decline in PHC relative to placebo (hazard ratio, 0.84 [95% CI, 0.74 to 0.96]). Corresponding hazard ratios for ≥10-unit decline in MHC and kidney disease symptoms, effects, and burden were 0.95 (95% CI, 0.85 to 1.07), 0.84 (95% CI, 0.75 to 0.94), 0.84 (95% CI, 0.72 to 0.97), and 0.93 (95% CI, 0.84 to 1.02), respectively. Conclusions In participants with CKD with and without type 2 diabetes, treatment with dapagliflozin slowed the decline in physical health, reduced worsening of symptoms, and lessened the effect of kidney disease. Clinical Trial registry name and registration number: Dapagliflozin and Prevention of Adverse Outcomes in CKD, NCT03036150. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2025_11_11_ASN0000000776.mp3