Nephroprotective Effects of Dapagliflozin in Patients with Type 2 Diabetes

Abstract

Objective This study analyzed changes in the estimated glomerular filtration rate calculated using cystatin C (eGFRcys) and sodium excretion in the urine after administering dapagliflozin as an add-on therapy to conventional treatment for diabetes. Methods This was a single-center, single-group, prospective interventional study. Dapagliflozin was administered to improve the plasma glucose control in 30 subjects with type 2 diabetes mellitus (age 53±8 years old; 66.6% men). Blood and urine tests were performed before and 6 and 12 months after dapagliflozin administration. The daily sodium excretion was estimated with the Kawasaki formula using second-morning urine samples. Results The eGFRcys did not markedly differ before and 6 months after the dapagliflozin administration but was significantly increased after 12 months (p<0.001), and the estimated daily sodium excretion was also significantly increased (p<0.001 at 6 months and p=0.002 at 12 months). The systolic and diastolic blood pressures tended to decrease after administration. The HbA1c level after the administration of dapagliflozin tended to be lower in the T3 group, showing the smallest increase in changes in the estimated daily sodium excretion from baseline to 6 months (28.2-107.5 mEq/day), than in the combined groups of T1 (219.5-110.1 mEq/day) and T2 (101.4-28.9 mEq/day). In contrast, the eGFRcys was significantly higher in the combined groups of T1 and T2 than that in the T3 group at both 6 and 12 months (p=0.031 and p=0.007, respectively). Conclusions Add-on therapy with dapagliflozin increased the urinary sodium excretion and decreased the blood pressure even in the early phase of this therapy. Our results suggest that dapagliflozin add-on therapy may exert nephroprotective effects in subjects with type 2 diabetes mellitus.

Keywords: dapagliflozin; diabetes mellitus; nephroprotective effects; sodium excretion; sodium glucose cotransporter-2.

Figure 1.

Significantly increased estimated daily sodium excretion in subjects with type 2 diabetes after 6 months of dapagliflozin treatment. The estimated glomerular filtration rate calculated using cystatin C (eGFRcys) did not significantly change within the first 6 months but was significantly increased after 12 months. Hence, the eGFRcys may be improved by a reduced kidney load. The urine albumin-to-creatinine ratio showed a decreasing trend with dapagliflozin treatment.

Figure 2.

Changes in HbA1c and eGFRcys levels and the urine albumin-to-creatinine ratio after add-on treatment with dapagliflozin between subjects with increased urine sodium excretion and those with almost no increase in urine sodium excretion. The change in HbA1c level was high, but not significantly so, in the T3 group, whereas the increase in the eGFRcys was significantly higher in the T3 group at both 6 and 12 months after treatment than before. Furthermore, the eGFRcys was higher at 12 months than at 6 months in both groups. In addition, the urine albumin-to-creatinine ratios tended to be lower in T1/T2 than in T3.