For adult patients with type 2 diabetes who are recovering from dialysis-requiring acute kidney injury (AKI-D), initiating sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy within 30 days of discharge is associated with fewer adverse kidney events compared with later initiation, as shown in a retrospective study.
Using a target trial emulation among 1,912 propensity-score matched pairs of adults with type 2 diabetes recovering from AKI-D, adverse kidney events occurred in 3.9 percent of patients who received an SGLT-2 inhibitor prescription within 30 days after discharge (early SGLT-2 initiation group) vs 6.2 percent of those who received a prescription 31–90 days after discharge (late SGLT-2 initiation group). The mean follow-up was 3.4 years. [JAMA Netw Open 2026;9:e2631231]
Early initiation of SGLT-2 inhibitor therapy was associated with a 38-percent reduction in the risk of adverse kidney events compared with late initiation (adjusted hazard ratio [aHR], 0.62, 95 percent confidence interval [CI], 0.46–0.83; p=0.001).
In the component analysis of adverse kidney events, the benefit observed with early vs late SGLT-2 inhibitor therapy initiation was primarily driven by preservation of kidney function, as reflected by a lower incidence of progression to eGFR <15 mL/min/1.73 m2 (3.4 percent vs 5.3 percent; aHR, 0.65, 95 percent CI, 0.48–0.89; p=0.006). These was no significant effect seen on the incidence of reinitiation of dialysis (1 percent vs 0.9 percent; aHR, 0.98, 95 percent CI, 0.73–1.30; p=0.87).
Results for all-cause mortality (aHR, 1.06, 95 percent CI, 0.84–1.35; p=0.63), major adverse cardiovascular events (aHR, 1.03, 95 percent CI, 0.80–1.34; p=0.81), or recorded 6-month safety outcomes did not significantly differ between the early and late SGLT-2 initiation groups.
“These findings extend previous evidence supporting SGLT-2 inhibitors after acute kidney disease by suggesting that the timing of initiation during the early post-discharge recovery phase may influence subsequent kidney outcomes, highlighting a potentially modifiable therapeutic window after severe AKI,” the authors noted.
They, however, cautioned against interpreting the findings as establishing a universal 30-day biological threshold but rather as supporting further investigation of post-discharge timing during the high-risk transition from AKI to acute kidney disease and chronic kidney disease.
“The question of when to initiate or resume kidney-protective therapy after AKI remains clinically challenging,” they said. “Clinicians may defer SGLT-2 inhibitor prescription during the post-AKI recovery period because of concerns regarding volume status, haemodynamic changes, ketoacidosis, recurrent kidney injury, or incomplete kidney recovery.”
The authors highlighted the need for prospective randomized clinical trials to establish the optimal timing, efficacy, and safety of SGLT-2 inhibitor treatment in the present population.
The retrospective target trial emulation used TriNetX electronic health record data from 2015 to 2024. The authors identified adults with type 2 diabetes who were hospitalized for AKI-D, had dialysis discontinued after discharge, and had no SGLT-2 inhibitor prescription in the prior year.
The mean age of the patients was 63 years, 57.9 percent were male, and 60.9 percent were White. Patient comorbidities were similar between the early and late SGLT-2 initiation groups. The most common recorded causes of AKI were sepsis-related injury (26.1 percent and 28.7 percent, respectively) and hypovolemia (25 percent and 29.7 percent, respectively).
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 eGFR <15 mL/min/1.73 m2.