Kidney-protective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) are supported by both randomized control trials and real world evidence in high cardiorenal risk type 2 diabetes mellitus (T2DM) patients. However, long-term efficacy studies of T2DM patients with normal kidney function and low cardiorenal risk are lacking. Using a large Israeli database we studied kidney outcomes in patients with T2DM with low baseline KDIGO risk (eGFR≥60 ml/min/1.73, UACR<30 mg/g) and no cardiovascular history. Patients who initiated empagliflozin or any SGLT2i during 2015-2021 were propensity score matched to DPP4i initiators by 120 baseline characteristics and followed until an event or end of study period. The primary outcome included a composite of ≥40% sustained eGFR decline, end-stage kidney disease (ESKD) , or all cause death. Risk was calculated using cox-proportional hazard models adjusted to baseline eGFR. At baseline, 5195 matched pairs of empagliflozin or DPP4i initiators had a mean age of 60 Y, mean eGFR of 93 mL/min/1.73 m2 and were followed for a median of 35.2 months. Number of events for composite kidney outcomes was 172 (11.0 events per 1000 patient-years [PY]) in the empagliflozin group and 215 (13.7 events per 1000 PY) in the DPP4i group, HR 0.79 (95% CI 0.65-0.97; p=0.02) . Similar trends were observed for composite of ≥40% sustained eGFR decline or ESKD. Comparing all SGLT2 to DPP4i initiators (n= 6477, median FU time 37.6 months) number of events was 2 (9.9 events per 1000 PY) for SGLT2i and 266 (13.0 events per 1000 PY) in DPP4i, HR 0.77 (95% CI 0.64-0.92) .
In conclusion the benefits of empagliflozin and any SGLT2 inhibitors on kidney function are observed in T2DM patients with low cardiorenal risk. The finding supports use of empagliflozin independent of glycemic control in low cardiorenal T2DM patients.
M.Schechter: None. C.Melzer cohen: None. A.Rozenberg: None. I.Yanuv: None. G.Chodick: None. O.Mosenzon: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, BOL Pharma, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Research Support; AstraZeneca, Novo Nordisk, Speaker's Bureau; AstraZeneca, Bayer AG, Eli Lilly and Company, Novo Nordisk, Sanofi. A.Karasik: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Vifor Pharma Management Ltd., Speaker's Bureau; Boehringer Ingelheim International GmbH, Novo Nordisk A/S.