(A-076) Continuation versus discontinuation of SGLT2is and cardiorenal outcomes among patients with type 2 diabetes and chronic kidney disease: a nationwide cohort study with a target trial emulation framework

Background: Clinical guidelines recommend continuation of sodium-glucose cotransporter-2 inhibitors (SGLT2is) treatment even when renal function deteriorates among patients with type 2 diabetes. However, the recommendation is not currently supported by research specifically designed to compare continuation versus discontinuation of SGLT2is for patients who have received the treatment for a while but experienced renal deterioration.

Objectives: We examined the association between SGLT2i continuation and major cardiorenal outcomes after estimated glomerular filtration rate (eGFR) decreased to below 45 mL/min/1.73 m2 among patients with type 2 diabetes and treated with SGLT2is.

Methods: We conducted a nationwide cohort study with a target trial emulation framework in a linked Taiwanese database that included claims and clinical data. We identified patients with type 2 diabetes who received SGLT2is during 2016-2020 and either continued or discontinued SGLT2is within 180 days after their eGFR declined to below 45 mL/min/1.73 m2. The study outcomes included myocardial infarction, stroke, heart failure, acute kidney injury, and all-cause mortality. The on-treatment and intention-to-treat hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated comparing SGLT2i continuation versus SGLT2i discontinuation, adjusting for baseline and time-varying covariates using inverse probability weighting.

Results: Among 11,467 eligible patients (7,743 for SGLT2i continuation and 3,724 for SGLT2i discontinuation), the on-treatment HR associated with SGLT2i continuation was 0.83 (95% CI, 0.59-1.18) for myocardial infarction, 0.74 (0.56-0.95) for stroke, 0.58 (0.49-0.69) for heart failure, 0.53 (0.45-0.63) for acute kidney injury, and 0.51 (0.42-0.61) for all-cause mortality. The intention-to-treat HR was 1.09 (0.81-1.45) for myocardial infarction, 0.85 (0.68-1.06) for stroke, 0.80 (0.68-0.93) for heart failure, 0.70 (0.61-0.82) for acute kidney injury, and 0.78 (0.67-0.90) for all-cause mortality. The results did not change meaningfully in several pre-specified subgroup analyses, including patients with eGFR below 30 mL/min/1.73 m2 or with a history of acute kidney injury.

Conclusions: Our findings derived from a sizable Asian diabetic population support continuing SGLT2i treatment when eGFR declines to below 45 mL/min/1.73 m2 given potential cardiovascular and survival benefits without an increased risk of acute kidney jury.