#1720 Insights from sodium-glucose transport 2 (SGLT2) inhibitors treatment in patients with systemic lupus erythematosus
Authors: Kenis Irina , Tayer-Shifman Oshrat E , Bar-Ziv Dorin , Kabaha Mohamad , Pri-Paz-Basson Yael , Kivity Shaye , Cohen-Hagai Keren , Benchetrit Sydney 
Published: May 2024

Abstract

Background and Aims
Kidney involvement is common among patients with systemic lupus erythematosus (SLE) and it is an important cause of morbidity and mortality among this population. Recently, the EULAR 2023 update of the recommendations for the management of SLE advised considering the use of sodium-glucose transport 2 inhibitors (SGLT2i) as kidney protective agents in patients with chronic kidney disease with reduced glomerular filtration rate (GFR). Aims: To assess clinical characteristics and outcomes of Israeli patients with SLE treated with SLGT2i.

Method
This retrospective study, conducted between 2014–2023, included adult patients with SLE diagnosed for at least 12 months. Patients receiving SGLT2i for a duration of three months or longer were compared with a control group consisting of patients who were not treated with these agents. Associated variables were assessed including disease-related characteristics, kidney-related factors, and comorbidities such as diabetes and heart failure. Clinical outcomes including severe infections, hospitalizations, and all-cause mortality were recorded. Repeated measures analysis model was applied to compare the estimated GFR (eGFR) at different time points (before diagnosis, at diagnosis, and at the last follow-up), among the SGLT2i-treated patients and controls. Protein to creatinine ratio was compared before starting treatment with SGLT2i and on treatment at the last follow-up.

Results
A total of 165 consecutive patients were included in this analysis, with a mean follow-up from SLE diagnosis of 15.6 ± 11.8 years. Of them, 7 were treated chronically with SGLT2i and had available data. While age at SLE diagnosis was comparable between the two groups (29.8 ± 12.2 years in the SGLT2i group and 32.6 ± 14.3 years in controls, p = 0.6), SGLT2i treated patients were significantly older at last follow-up (62.1 ± 13.5 years vs. 47.3 ± 16.3 years, p = 0.019), and as a consequence, the duration of follow-up since SLE diagnosis was longer among them (26.2 ± 11 years vs. 15.3 ± 11.7 years in the controls, p = 0.04). Diabetes was diagnosed in 16 out of 165 patients (9.7%), and 5 out of 7 patients treated with SGLTi were diabetic (71.4% vs. 7.0% in controls, p &lt; 0.01). Heart failure was diagnosed in 7.3% of the cohort, and was more prevalent among the SGLTi group (28.6% vs 6.3% in controls, p = 0.03). Only 26.6% of patients with diabetes and 16.7% of patients with heart failure were treated with SGLTi.
On repeated measures analysis, eGFR decreased significantly during the study period (p = 0.043, Fig. 1). The decline in eGFR throughout the study period was comparable between the groups.
Protein to creatinine ratio decreased significantly in the SGLTi-treated patients after starting treatment (1516 ± 1685 mg/g before treatment vs. 611 ± 875 mg/g after treatment, p = 0.05).
The prevalence of severe infections requiring hospitalization was comparable between groups (28.6% in SGLTi vs 29.9% in controls, p = 0.9). Hospitalizations for SLE exacerbations, as well as hospitalization for cardiovascular events, were similarly comparable between groups (28.6% vs, 28.5%, p = 0.9 and 14.3% vs. 15.3%, p = 0.9; respectively). During the study period, 10 patients developed end-stage kidney disease and 11 patients died, with no significant difference between groups.

Conclusion
While the SGLT2i-treated patients were older and had higher rates of comorbidities such as diabetes, chronic kidney disease, and heart failure, a similar rate of kidney function decline was observed in both SGLT2i-treated patients and controls. Additionally, a comparable rate of severe infections was found in both groups of patients. This relatively small cohort could support the use of these kidney and heart protective agents in patients with SLE and kidney involvement. A special consideration should be given to patients with comorbid diabetes and heart failure.