Early Sodium-Glucose Cotransporter-2 Inhibitor Use After Acute Kidney Injury in Type 2 Diabetes

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve kidney and cardiovascular outcomes in type 2 diabetes, chronic kidney disease, and heart failure, but optimal initiation timing after dialysis-requiring acute kidney injury (AKI-D) is uncertain.

To compare outcomes associated with SGLT-2 inhibitor prescription within 30 days vs 31 to 90 days after discharge among adults with type 2 diabetes recovering from AKI-D.

This cohort study using a target trial emulation design used TriNetX Global Collaborative Network electronic health records from January 1, 2015, to September 1, 2024. Eligible adults had type 2 diabetes, were hospitalized for AKI-D, had dialysis discontinued after discharge, and had no SGLT-2 inhibitor prescription in the prior year.

First documented SGLT-2 inhibitor prescription within 30 days after discharge vs 31 to 90 days after discharge.

Primary outcomes were adverse kidney events, all-cause mortality, and major adverse cardiovascular events. Adverse kidney events included dialysis reinitiation, incident end-stage kidney disease, or recorded estimated glomerular filtration rate less than 15 mL/min/1.73 m2. Selected 6-month safety outcomes were also assessed. A 90-day landmark design and 1:1 propensity score matching were used.

Among 4406 eligible patients before propensity score matching, 2268 initiated SGLT-2 inhibitors within 30 days (mean [SD] age, 63.5 [12.9] years; 1336 male [58.9%]), and 2138 initiated SGLT-2 inhibitors between 31 and 90 days (mean [SD] age, 62.7 [13.5] years; 1210 male [56.6%]). After 1:1 propensity score matching, 1912 patients remained in each group (mean [SD] age, 63.0 [13.0] vs 62.8 [13.5] years; 1102 [57.6%] vs 1112 [58.2%] male, in the early vs late SGLT-2 initiation groups, respectively). During a mean follow-up of 3.4 years (IQR, 1.1-3.3 years), early prescription was associated with a lower risk of adverse kidney events compared with late prescription in 74 patients (3.9%) vs 119 patients (6.2%) (adjusted hazard ratio [AHR], 0.62; 95% CI, 0.46-0.83). All-cause mortality (AHR, 1.06; 95% CI, 0.84-1.35; P = .63) and major adverse cardiovascular events (AHR, 1.03; 95% CI, 0.80-1.34; P = .81) did not differ significantly. Recorded 6-month safety outcomes were also similar.

In adults with type 2 diabetes recovering from AKI-D, SGLT-2 inhibitor prescription within 30 days after discharge was associated with fewer adverse kidney events than prescription at 31 to 90 days, without significant differences in mortality, cardiovascular events, or recorded short-term safety outcomes. These findings support timely initiation of SGLT-2 inhibitors during the post-AKI recovery period and provide a rationale for prospective randomized clinical trials.