Comparing SGLT2 Inhibitors on Incident Major Adverse Kidney Events in Type 2 Diabetes: A Target Trial Emulation

To determine whether canagliflozin, dapagliflozin, and empagliflozin differ in rates of major adverse kidney events (MAKE) in adults with T2D at moderate cardiovascular risk and without stage 3+ chronic kidney disease (CKD) at baseline.

Using target trial emulation and U.S. claims data from commercial, Medicare Advantage, and traditional Medicare plans, we compared canagliflozin, dapagliflozin, and empagliflozin among adults ≥ 21years with T2D at moderate cardiovascular risk (1-5% annualized MACE or death risk), without insulin use or stage 3+ chronic kidney disease (CKD) at baseline, initiating treatment from January 1, 2014, and December 31, 2021. Propensity scores estimated via super learner ensemble were incorporated as inverse probability weights into Cox models examining major adverse kidney events (MAKE: stage 3+ CKD, kidney failure, kidney replacement therapy initiation) and all-cause death under intention-to-treat analysis through December 31, 2022.

The weighted cohort included 41,248, 17,548, and 72,638 adults initiating canagliflozin, dapagliflozin, and empagliflozin, respectively. One-year post-initiation, rates of MAKE were 3.2% in the dapagliflozin and empagliflozin arms and 3.5% in the canagliflozin arm; by three years, 8.4%, 8.5%, and 9.1%. Compared to canagliflozin, MAKE risk was lower with dapagliflozin (HR 0.91; 95%CI 0.85-0.97) and empagliflozin (HR 0.93; 95%CI 0.88-0.97), with no difference between dapagliflozin and empagliflozin.

Empagliflozin and dapagliflozin were associated with modestly lower adverse kidney event rates compared to canagliflozin. These findings provide clinically actionable evidence to support selection of SGLT2i to reduce CKD risk in a highly prevalent subset of people with T2D.