Background/Purpose: Systemic lupus erythematosus (SLE) is associated with increased risks of cardiovascular events, renal complications, and premature mortality. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have shown cardiorenal benefits in diabetic populations, but their impact among patients with both SLE and diabetes remains unclear.

Methods: This retrospective cohort study utilized data from the global TriNetX Collaborative Network and included adult patients (aged ≥18 years) diagnosed with systemic lupus erythematosus (SLE) and diabetes, with or without exposure to sodium-glucose co-transporter-2 (SGLT2) inhibitors, between January 1, 2015, and December 31, 2023. Patients were grouped based on receipt of SGLT2 inhibitors. The primary outcome was all-cause mortality, while secondary outcomes included major adverse cardiovascular events (MACE) and incidence of lupus nephritis over one year. Propensity score matching was employed to balance baseline characteristics between the SGLT2 and non-SGLT2 groups. Risk ratios and 95% confidence intervals (CIs) were calculated for univariable comparisons of outcomes after matching.

Results: After propensity score matching, 1,024 patients were included in each group. The overall cohort’s mean ± SD age was 58.4 ± 12.4 years, with 80% female and the majority identifying as White (approximately 36%). Matching achieved balance across cohorts (standardized differences < 0.1 for key demographics). The incidence of major adverse cardiovascular events (MACE) was lower in the SGLT2 group compared to the non-SGLT2 group (4.3% vs. 6.1%; risk ratio [RR], 0.71; 95% CI, 0.487–1.034; p = 0.0726), though not statistically significant. All-cause mortality was significantly lower in the SGLT2 group (4.7% vs. 7.8%; RR, 0.60; 95% CI, 0.424–0.849; p = 0.0035). However, the incidence of lupus nephritis was significantly higher in the SGLT2 group compared to the non-SGLT2 group (11.3% vs. 5.0%; RR, 2.28; 95% CI, 1.655–3.125; p < 0.0001).

Conclusion: Among patients with SLE and diabetes, treatment with SGLT2 inhibitors was associated with a significant reduction in all-cause mortality but an increased risk of lupus nephritis. Although a trend toward fewer cardiovascular events was observed, it did not reach statistical significance. These findings highlight the need for careful benefit-risk assessment when prescribing SGLT2 inhibitors in this population and underscore the importance of further prospective studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-sglt2-inhibitors-on-cardiovascular-events-mortality-and-lupus-nephritis-in-patients-with-systemic-lupus-erythematosus-and-diabetes-retrospective-cohort-study/