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Multicenter Study
. 2024 Jun 3;7(6):e2416578.
doi: 10.1001/jamanetworkopen.2024.16578.

Sodium-Glucose Cotransporter-2 Inhibitors and Nephritis Among Patients With Systemic Lupus Erythematosus

Fu-Shun Yen  1 , Shiow-Ing Wang  2   3 , Chih-Cheng Hsu  4   5   6   7 , Chii-Min Hwu  8   9 , James Cheng-Chung Wei  3   10   11
Affiliations
Multicenter Study

Sodium-Glucose Cotransporter-2 Inhibitors and Nephritis Among Patients With Systemic Lupus Erythematosus

Fu-Shun Yen et al. JAMA Netw Open. .

Abstract

Importance: Lupus nephritis is a major complication of systemic lupus erythematosus (SLE). Randomized clinical trials have shown nephroprotective and cardioprotective effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is).

Objective: To investigate whether the use of SGLT2is is associated with the onset and progression of lupus nephritis and other kidney and cardiac outcomes in patients with SLE and type 2 diabetes.

Design, setting, and participants: This multicenter cohort study used the US Collaborative Network of the TriNetX clinical data platform to identify patients with SLE and type 2 diabetes from January 1, 2015, to December 31, 2022. Data collection and analysis were conducted in September 2023.

Exposures: Individuals were categorized into 2 groups by SGLT2i use or nonuse with 1:1 propensity score matching.

Main outcomes and measures: The Kaplan-Meier method and Cox proportional hazards regression models were used to calculate the 5-year adjusted hazard ratios (AHRs) of lupus nephritis, dialysis, kidney transplant, heart failure, and mortality for the 2 groups.

Results: From 31 790 eligible participants, 1775 matched pairs of SGLT2i users and nonusers (N = 3550) were selected based on propensity scores. The mean (SD) age of matched participants was 56.8 (11.6) years, and 3012 (84.8%) were women. SGLT2i users had a significantly lower risk of lupus nephritis (AHR, 0.55; 95% CI, 0.40-0.77), dialysis (AHR, 0.29; 95% CI, 0.17-0.48), kidney transplant (AHR, 0.14; 95% CI, 0.03-0.62), heart failure (AHR, 0.65; 95% CI, 0.53-0.78), and all-cause mortality (AHR, 0.35; 95% CI, 0.26-0.47) than SGLT2i nonusers.

Conclusions and relevance: In this cohort study of patients with SLE and type 2 diabetes, SGLT2i users had a significantly lower risk of lupus nephritis, dialysis, kidney transplant, heart failure, and all-cause mortality than nonusers. The findings suggest that SGLT2is may provide some nephroprotective and cardioprotective benefits.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Flowchart of the Selection Process
SGLT2i indicates sodium-glucose cotransporter-2 inhibitor; SLE, systemic lupus erythematosus; T2D, type 2 diabetes.
Figure 2.
Figure 2.. Event-Free Survival Probabilities
SGLT2i indicates sodium-glucose cotransporter-2 inhibitor.
Figure 3.
Figure 3.. Subgroup Analyses of the Risk of Incident Lupus Nephritis by Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) Use
To convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01; creatinine to μmol/L, multiply by 88.4. CKD indicates chronic kidney disease; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin.
See this image and copyright information in PMC

References

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