SGLT2 Inhibitors Significantly Improve Kidney and Cardiac outcomes in SLE Patients with Type 2 Diabetes: JAMA

In this multicenter cohort study involving 1,775 matched pairs of SGLT2 inhibitor users and non-users with SLE and type 2 diabetes, the use of SGLT2 inhibitors was associated with a significantly lower risk of dialysis, lupus nephritis, heart failure, kidney transplant, and all-cause mortality compared to those not using SGLT2 inhibitors, the researchers reported in JAMA Network Open.

Systemic lupus erythematosus is a chronic and potentially life-threatening autoimmune disease that arises when the body’s immune system loses tolerance to its nuclear antigens. Patients with SLE experience mortality rates that are about 2.2 times higher than those of individuals without the condition. Lupus nephritis is a major complication of SLE. Randomized clinical trials have shown cardioprotective and nephroprotective effects of sodium-glucose cotransporter-2 inhibitors.

Against the above background, Fu-Shun Yen, Dr Yen’s Clinic, Taoyuan, Taiwan, and colleagues aimed to investigate whether SGLT2is use is associated with the onset and progression of lupus nephritis and other cardiac and kidney outcomes in patients with SLE and type 2 diabetes.

The multicenter cohort study utilized the US Collaborative Network of the TriNetX clinical data platform to identify patients with systemic lupus erythematosus and type 2 diabetes from 2015 to 2022. Data collection and analysis were conducted in September 2023.

Participants were divided into two groups based on SGLT2 inhibitor use or non-use, employing 1:1 propensity score matching.

The study used the Kaplan-Meier method and Cox proportional hazards regression models to determine the 5-year adjusted hazard ratios (AHRs) for lupus nephritis, dialysis, kidney transplantation, heart failure, and mortality between the two groups.

The study revealed the following findings:

• From 31,790 eligible participants, 1775 matched pairs of SGLT2i users and nonusers (N = 3550) were selected based on propensity scores.
• The mean age of matched participants was 56.8 years, and 84.8% were women.
• SGLT2i users had a significantly lower risk of lupus nephritis (AHR, 0.55), dialysis (AHR, 0.29), kidney transplant (AHR, 0.14), heart failure (AHR, 0.65), and all-cause mortality (AHR, 0.35) than SGLT2i nonusers.

The findings showed that SGLT2i use in patients with SLE and type 2 diabetes is tied to a significantly reduced risk of dialysis, lupus nephritis, kidney transplant, heart failure, and all-cause mortality compared with SGLT2i nonuse.

"SGLT2is may provide some cardioprotective and nephroprotective benefits in patients with SLE and type 2 diabetes. However, more rigorous, prospective RCTs are needed to confirm these findings," the researchers concluded.

Reference:

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