Objective:
Daprodustat is a novel oral agent in treating
anemia of
chronic kidney disease (CKD), and several clinical trials have been conducted to compare
daprodustat with recombinant human
erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of
daprodustat for
anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients. Methods: Six databases were searched for randomized controlled trials (RCTs) reporting
daprodustat vs. rhEPO or placebo for
anemia patients in CKD. The outcome indicators were focused on
hemoglobin (Hb),
ferritin,
transferrin saturation (TSAT), total
iron-binding capacity (TIBC),
vascular endothelial growth factor (
VEGF), and serious adverse events (SAEs). Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in
daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between
daprodustat and rhEPO group (MD = 0.05, [95% CI, -0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, -0.28 to 0.52], p = 0.55; respectively). The indexes of
iron metabolism were improved significantly in the
daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma
VEGF was observed in
daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between
daprodustat and placebo treatment, while the incidence of SAEs in the
daprodustat group was significantly lower than that in the rhEPO group. Conclusion:
Daprodustat was efficacious and well tolerated for
anemia in both NDD and DD patients in the short term based on current RCTs. And
daprodustat may become an effective alternative for treatment of
anemia with CKD. Since the application of
daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of
daprodustat.