New Study Shows SGLT2 Inhibitors Reduce Cardiorenal Risks in Patients with Lupus and Diabetes

Patients with SLE are already at an increased risk for cardiovascular and renal issues, and the presence of T2D exacerbates these risks. SLE patients were not included in clinical trials for SGLT2i, leaving uncertainty about whether the cardiorenal benefits of these medications apply to those with SLE and concurrent T2D. Karen H. Costenbader, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, and colleagues aimed to investigate whether SGLT2 inhibitors could offer additional protective benefits in this vulnerable population.

For this purpose, the researchers conducted an emulated clinical trial within an insurance-based cohort in the US. They evaluated the effectiveness of SGLT2 inhibitors compared to DPP4 inhibitors for the primary prevention of cardiovascular, renal, and other clinical outcomes in patients with SLE and comorbid type 2 diabetes. To ensure comparability, SGLT2i initiators were matched with DPP4i initiators using propensity scores that accounted for various clinical and demographic factors. Hazard ratios (HR) were calculated through Cox models to assess the outcomes.

The study revealed the following findings:

• Comparison was made between 2,165 patients starting SGLT2 inhibitors (SGLT2i) and 2,165 propensity score-matched patients starting dipeptidyl peptidase 4 inhibitors (DPP4i).

• Over an average of 753.1 days, SGLT2i recipients exhibited:

• Significantly lower risk of incident acute kidney injury (HR 0.49).

• Reduced risk of chronic kidney disease (HR 0.61).

• Lower risk of end-stage renal disease (HR 0.40).

• Decreased risk of heart failure (HR 0.72).

• Fewer emergency department visits (HR 0.90).

• No significant differences were found in:

• All-cause mortality (HR 0.89).

• Lupus nephritis (HR 0.67).

• Myocardial infarction (HR 0.81).

• Stroke (HR 1.03).

• Hospitalizations (HR 0.76).

•There was an increased risk of genital infections (HR 1.31), but the risk of urinary tract infection did not differ (HR 0.90).

• No significant differences were observed for diabetic ketoacidosis risk (HR 1.065) or fractures (HR 0.95).

"In the emulated clinical trial, the use of SGLT2 inhibitors compared to DPP4 inhibits was linked to significantly lower risks of various cardiorenal complications in patients with both systemic lupus erythematosus and type 2 diabetes," the researchers concluded.

Reference:

Sheng-Kai Ma, K., Lo, E., Kyttaris, V. C., Tsokos, G. C., & Costenbader, K. H. Efficacy and Safety of Sodium-Glucose Co-Transporter 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. Arthritis & Rheumatology. https://doi.org/10.1002/art.43037