SGLT2 Inhibitors Could Reduce Risk of Lupus Nephritis and Dialysis in Systemic Lupus Erythematosus

James Cheng-Chung Wei, PhD
Credit: LinkedIn

Use of SGLT2 inhibitors in patient with type 2 diabetes and lupus was linked to a reduction in risk of nephritis, dialysis, transplant, and mortality, according to a new analysis.¹

“Our study suggests that SGLT2is may provide multiple benefits beyond glycemic control, including nephroprotection and cardioprotection in patients with both SLE and type 2 diabetes,” investigators wrote.¹

In the last decade, the SGLT2 inhibitor class has been thrust into the spotlight with revelations of their cardiorenal protective benefit expanding their scope of use beyond glycemic control in people with type 2 diabetes. As indications for the class have grown, so too has the interest in exploring their potential benefits beyond these conditions, including gout.^2,3

A team led by James Cheng-Chung Wei, PhD, vice superintendent at the Chung Shan Medical University Hospital, launched the current study to explore the relationship between SGLT2 inhibitor use and risk of adverse events among patients with type 2 diabetes and systemic lupus erythematosus (SLE). With this in mind, the study was designed as a propensity score matched analysis of data from patients within the TriNetX database. Containing data from more than 250 million individual patients, the database provided investigators with information from 31 790 patients with type 2 diabetes and SLE who received care between January 1, 2015, to December 31, 2022.¹

Following propensity score matching using TriNetX’s built-in capability to generate propensity scores and 1:1 matching using greedy nearest neighbor matching, a total of 1775 matching pairs of SGLT2 inhibitor users and nonusers were identified for inclusion. This cohort had a mean age of 56.8 (SD, 11.6) years, 13.5% were men, and 55.8% were White.¹

The primary outcome of interest for the investigators’ analyses was the difference in the 5-year risk for each of the following adverse outcomes: lupus nephritis, dialysis, kidney transplant, heart failure, and mortality. Investigators pointed out 5-year risk was estimated using Kaplan-Meier method and Cox proportional hazards regression models.¹

Upon analysis, investigators observed a reduction in risk for lupus nephritis (adjusted Hazard Ratio [aHR], 0.55; 95% Confidence Interval [CI], 0.40 to 0.77), dialysis (aHR, 0.29; 95% CI, 0.17 to 0.48), kidney transplant (aHR, 0.14; 95% CI, 0.03 to 0.62), heart failure (aHR, 0.65; 95% CI, 0.53 to 0.78), and all-cause mortality (aHR, 0.35; 95% CI, 0.26-0.47) among patients receiving SGLT2 inhibitors relative to their matched counterparts not receiving SGLT2 inhibitors. In competing risk analyses using death as a competing risk, SGLT2 inhibitor use was associated with a reduced risk of lupus nephritis (aHR, 0.43; 95% CI, 0.35 to 0.54), dialysis (aHR, 0.34; 95% CI, 0.26 to 0.44), kidney transplant (aHR, 0.33; 95% CI, 0.25 to 0.45), heart failure (aHR, 0.57; 95% CI, 0.48 to 0.68), and all-cause mortality (aHR, 0.35; 95% CI, 0.26 to 0.47) relative to no SGLT2 inhibitor use.¹

Investigators noted multiple limitations within their study to consider before overinterpretation of study results. These included challenges in achieving optimal matching, possibility for missing or incomplete data on patients with mild or asymptomatic SLE or lupus nephritis leading to bias, reliance on ICD-10-CM codes to identify incidence of lupus nephritis without confirmation by biopsy, and the retrospective nature of the study design.¹

“SGLT2is may provide some nephroprotective and cardioprotective benefits in patients with SLE and type 2 diabetes. However, these findings need to be confirmed by more rigorous, prospective [randomized controlled trials],” investigators added.¹

References:

1. ^{Yen F, Wang S, Hsu C, Hwu C, Wei JC. Sodium-Glucose Cotransporter-2 Inhibitors and Nephritis Among Patients With Systemic Lupus Erythematosus. JAMA Netw Open. 2024;7(6):e2416578. doi:10.1001/jamanetworkopen.2024.16578}
2. ^{Campbell P, Iapoce C. 10 years of SGLT2 inhibitors: A Decade of Redefining Cardiometabolic Care. HCP Live. March 29, 2023. Accessed June 12, 2024. https://www.hcplive.com/view/10-years-of-sglt2-inhibitors-a-decade-of-redefining-cardiometabolic-care.}
3. ^{Campbell P. For people with diabetes, starting an SGLT2 inhibitor could lower gout risk. HCP Live. June 4, 2023. Accessed June 12, 2024. https://www.hcplive.com/view/for-people-with-diabetes-sglt2-inhibitor-could-lower-gout-risk.}