A real-world study on SGLT2 inhibitors and diabetic kidney disease progression

BACKGROUND: Randomized controlled trials have demonstrated the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2is) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, real-world data on CKD progression and the development of end-stage kidney disease (ESKD) remains scarce. Our aim was to study renal outcomes of people with diabetic kidney disease (DKD) using SGLT2is in a highly prevalent DKD population. METHODS: Between 2016 and 2019 we recruited T2DM patients in the renal and diabetic clinics in a regional hospital in Singapore. Patients prescribed SGLT2is were compared with those on standard anti-diabetic and renoprotective treatment. The outcome measures were CKD progression [a ≥25% decrease from baseline and worsening of estimated glomerular filtration rate (eGFR) categories according to the Kidney Disease: Improving Global Outcomes guidelines] and ESKD (eGFR <15 mL/min/1.73 m(2)). RESULTS: We analysed a total of 4446 subjects; 1598 were on SGLT2is. There was a significant reduction in CKD progression {hazard ratio [HR] 0.60 [95% confidence interval (CI) 0.49–0.74]} with SGLT2is. The HR for eGFR ≥45 mL/min/1.73 m(2) and 15–44 mL/min/1.73 m(2) was 0.60 (95% CI 0.47–0.76) and 0.43 (95% CI 0.23–0.66), respectively. There was also a reduction in risk for developing ESKD for the entire cohort [HR 0.33 (95% CI 0.17–0.65)] and eGFR 15–44 mL/min/1.73 m(2) [HR 0.24 (95% CI 0.09–0.66)]. Compared with canagliflozin and dapagliflozin, empagliflozin showed a sustained risk reduction of renal outcomes across CKD stages 1–4. CONCLUSIONS: This real-world study demonstrates the benefits of SGLT2is on CKD progression and ESKD. The effect is more pronounced in moderate to advanced CKD patients.