Efficacy and Safety of Sodium–Glucose Cotransporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events, and Safety Outcomes in Patients With Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-Based Target Trial Emulation

Abstract

Objective

Patients with systemic lupus erythematosus (SLE) were excluded from sodium–glucose cotransporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D).

Methods

We performed an emulated clinical trial in an insurance-based cohort in the United States, evaluating SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP4i) for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE and comorbid T2D. SGLT2i initiators were matched to DPP4i initiators using propensity scores (PSs) based on clinical and demographic factors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox models.

Results

Outcomes among 2,165 patients starting SGLT2i and 2,165 PS-matched patients starting DPP4i were compared. Over 753.1 (±479.2) mean days, SGLT2i recipients had significantly lower risks of incident acute kidney injury (HR 0.49, 95% CI 0.39–0.63), chronic kidney disease (HR 0.61, 95% CI 0.50–0.76), end-stage renal disease (HR 0.40, 95% CI 0.20–0.80), heart failure (HR 0.72, 95% CI 0.56–0.92), emergency department visits (HR 0.90, 0.82–0.99), and severe sepsis (HR 0.61, 95% CI 0.39–0.94). Risks of all-cause mortality (HR 0.89, 95% CI 0.65–1.21), lupus nephritis (HR 0.67, 95% CI 0.38–1.15), myocardial infarction (HR 0.81, 95% CI 0.54–1.23), stroke (HR 1.03, 95% CI 0.74–1.44), and hospitalizations (HR 0.76, 95% CI 0.51–1.12) did not differ. Genital infection risk (HR 1.31, 95% CI 1.07–1.61) was increased, but urinary tract infection risk (HR 0.90, 95% CI 0.79–1.03) did not differ. No significant difference was observed for diabetic ketoacidosis risk (HR 1.07, 95% CI 0.53–2.14) and fractures (HR 0.95, 95% CI 0.66–1.36).

Conclusion

In this emulated clinical trial, treatment with SGLT2i, compared to DPP4i therapy, was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2D.