Renal and Glucose-Lowering Effects of Empagliflozin and Dapagliflozin in Different Chronic Kidney Disease Stages

Abstract

Objective: The objective of this study was to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal function in different stages of chronic kidney disease (CKD). Design and Methods: We conducted a retrospective cohort study using longitudinal claims data from May 2016-December 2017 from the Chang Gung Research Database. Patients who used one of the three types of SGLT2 inhibitor available at Chang Gung Memorial Hospital, namely empagliflozin 10 mg/tab (Empa10), empagliflozin 25 mg/tab (Empa25), and dapagliflozin 10 mg/tab (Dapa), were included, with the same number of matched non-users. Analysis of variance was used for continuous variables and the chi-square test was applied for categorical variables. Differences in data between two groups were analyzed using an independent t-test, and the basic data before and after treatment were analyzed using generalized estimating equation (GEE). The association among renal function changes was analyzed using a Cox proportional hazards model, with the results presented as unadjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: Among the 7,624 SGLT2 inhibitor users, 1,696 patients used Empa10, 2,654 used Empa25, and 3,274 used Dapa. Compared with non-users, dapagliflozin had the lowest risk of estimated glomerular filtration rate (eGFR) decrease over 40% from baseline within 1 year (HR 0.36, 95% CI 0.25-0.51). By using the ICD-10-CM code N179, the acute kidney injury (AKI)-related hospitalization rate was lower in Empa10 and Dapa users than in non-users (HR 0.65, 95% CI 0.49-0.86). Conclusion: Lower risk of eGFR decrease over 40% and AKI-related hospitalization was found in all SGLT2 inhibitor users across the different CKD stages.

Keywords: Chang Gung Research Database; acute kidney injury; glucose control; renal function; sodium–glucose cotransporter 2 inhibitors.

Figure 1

Change in estimated glomerular filtration rate (eGFR), and glycated hemoglobin (HbA1c), and creatinine (Cre) levels in users of sodium–glucose cotransporter 2 (SGLT2) inhibitors and other drugs.

Figure 2

Change in estimated glomerular filtration rate (eGFR), and glycated hemoglobin (HbA1c), and creatinine (Cre) levels in empagliflozin and dapagliflozin users.

Figure 3

Change in estimated glomerular filtration rate (eGFR), and glycated hemoglobin (HbA1c), and creatinine (Cre) levels in empagliflozin 10 mg/tab, empagliflozin 25 mg/tab, and dapagliflozin 10 mg/tab users.

Figure 4

Cox proportional hazard models for decrease in eGFR over 40% in patients receiving sodium–glucose cotransporter 2 inhibitors and other drugs. The probability of a decrease in eGFR over 40% is shown for empagliflozin 10 mg/tab, empagliflozin 25 mg/tab, and dapagliflozin 10 mg/tab users vs. non-users in different renal function subgroups. eGFR, estimated glomerular filtration rate.

Figure 5

Decrease in eGFR over 40%-free survival rates in the patients with diabetes. The outcome was estimated using Cox regression models stratified according to history of eGFR decrease over 40% for SGLT2 inhibitor users vs. non-users. eGFR, estimated glomerular filtration rate; SGLT2i, sodium–glucose cotransporter 2 inhibitor.

Figure 6

Cumulative incidence rate of decrease in eGFR over 40% in patients with diabetes. Outcomes were estimated according to history of eGFR decrease over 40% for SGLT2 inhibitor users vs. non-users. eGFR, estimated glomerular filtration rate; SGLT2i, sodium–glucose cotransporter 2 inhibitor.

Figure 7

Cox proportional hazard models for AKI-related hospitalization rate in patients receiving sodium–glucose cotransporter 2 inhibitors and non-users. The probability of AKI-related hospitalization is shown for empagliflozin 10 mg/tab, empagliflozin 25 mg/tab, and dapagliflozin 10 mg/tab users vs. non-users in different renal function subgroups. AKI, acute kidney injury.

Figure 8

Cox proportional hazard models for AKI-related hospitalization in patients with different renal function levels. The probability of AKI-related hospitalization is shown for eGFR<15, 15–29, 30–59, and 60–89 mL/min/1.73 m² vs. eGFR ≥ 90 mL/min/1.73 m² in different SGLT2 inhibitor users and non-users. eGFR, estimated glomerular filtration rate; SGLT2i, sodium–glucose cotransporter 2 inhibitor.

Figure 9

AKI-related hospitalization-free survival rates in patients with diabetes. Outcomes were estimated using Cox regression models stratified according to history of hospitalization related to AKI for SGLT2 inhibitor users vs. non-users. eGFR, estimated glomerular filtration rate; SGLT2i, sodium–glucose cotransporter 2 inhibitor; AKI, acute kidney injury.