123-OR: SGLT2 Inhibitors Are Associated with Kidney Benefits at All Degrees of Proteinuria—A Cohort Study

Background: The kidney benefits of sodium-glucose lowering co-transporter 2 inhibitors (SGLT2i) in adults with non-severe albuminuria, under-represented in SGLT2i trials, are not well established.

Objective: We performed a retrospective cohort study to examine the effectiveness of SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP4i), in Alberta, Canada.

Methods: Using administrative data, we derived a cohort of SGLT2i new-users (2014-2018) with diabetes and eGFR ≥ 30 mL/min/1.73 m². New SGLT2i users were matched 1:2 to DPP4i users by CKD stage, albuminuria, and diabetes therapy, and by time-conditional propensity-score (age, sex, A1c, etc.). Non-severe albuminuria was defined as a urine albumin to creatinine ratio ≤ 30 mg/mmol. Linear and Poisson regression models were used to determine the association of SGLT2i use with each outcome: eGFR decline (acute [≤ 60 days] and total), adverse kidney events, and all-cause mortality. An adverse kidney event was defined as sustained 40% loss of eGFR, initiation of kidney replacement therapy, or death from kidney causes.

Results: SGLT2i users (n=19,238) had a mean age of 57.9 years (male 59.1%) and non-severe albuminuria in 94.4%. Mean eGFR was 91.7 mL/min/1.73m², and 62.0% were dispensed ACE inhibitor or ARB. Median follow-up was 1.58 years (IQR 0.91-2.49). The acute change in eGFR was -2.79 (SGLT2i) vs -1.43 (DPP4i), for a difference of -1.36 (95% CI -1.74-[-0.98], p < 0.001). After day 60, SGLT2i use was associated with 0.83 (0.66-1.01, p < 0.001) less annual eGFR loss than in DPP4i users. SGLT2i use was associated with fewer adverse kidney events (IRR 0.58 [0.47-0.71], p < 0.001), driven mostly by less sustained loss of eGFR, but was not associated with all-cause mortality (IR 0.82 [0.66-1.01], p = 0.06). Similar findings were observed in those with non-severe albuminuria.

Interpretation: SGLT2i may prevent eGFR decline and reduce the risk of adverse kidney events in adults with diabetes, regardless of baseline albuminuria status.