Discussion
CKD, inflammation, diabetic kidney disease, anemia, Inflammation, heart failure
DIABETIC KIDNEY DISEASE, INFLAMMATION, ANEMIA, IRON DEFICIENCY, INFLAMMATION, EVENTS, HEART FAILURE, TYPE 2 DIABETES
In this post-hoc analysis of the DELIGHT trial, dapagliflozin and a combination of dapagliflozin and saxagliptin increased hemoglobin/hematocrit and reduced ferritin in patients with type 2 diabetes and CKD. Dapagliflozin reduced urinary inflammatory markers, specifically MCP-1/Cr and IL-6/Cr.The effect on iron homeostasis with SGLT2 inhibition has been assessed in patients with heart failure [Dapagliflozin with and without saxagliptin reduced urinary inflammation markers of MCP-1/Cr and IL-6/Cr. Inflammation is strongly associated with diabetic kidney disease progression as well as cardiovascular events [The current study does not support the additive effect of saxagliptin on markers of hematopoiesis, iron and inflammation when used in combination with SGLT2 inhibitors. In the current study, the reduction in HbA1c was more pronounced in the combination dapagiliflozin-saxigliptin group compared to dapagliflozin alone, suggesting that the decreases in iron and inflammation markers with dapagliflozin observed in this study are unlikely mediated by improved glycemic control.Increased systemic inflammation worsens iron availability, partly via increased hepcidin [Limitations of this study include its post-hoc nature, which may increase chance findings. Secondly, the absence of hepcidin concentration precludes our ability to test the hypothesis that SGLT2 inhibition addresses functional iron deficiency by reducing hepcidin. Third, these analyses do not account for use of iron preparation or ESA therapy during the study. Possible unbalance in anemia treatment could bias the effect estimation on hematological and iron parameters, although the short follow up duration of 6 moths reduced that risk. Finally, urinary MCP-1 and IL-6 were measured in spot urine samples and indexed to urinary creatinine. This might decrease the precision of the observed effect estimates as the concentration of urinary analytes are more variable in spot urine than 24-hour samples. However, despite the potential decrease in statistical power, we observed statistically significant reduction in urinary inflammation markers.