SGLT2 inhibitors have ‘potential role’ in reducing cardiac, renal risks in lupus
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SAN DIEGO — Patients with lupus who received sodium-glucose cotransporter-2 inhibitors demonstrated reduced risks for major adverse cardiovascular events and kidney disease, a speaker said at ACR Convergence 2023.
April Jorge, MD, of Massachusetts General Hospital, and colleagues, noted that previous data in patients with type 2 diabetes showed that SGLT2 inhibitors may positively impact kidney and cardiovascular outcomes that are largely independent of glycemic control. “However, patients with lupus were excluded from clinical trials of those medications,” Jorge told attendees.
To determine the impact of SGLT2 inhibitors vs. a comparator oral hypoglycemic agent — in this case, dipeptidyl peptidase 4 (DPP4) inhibitors — on kidney and cardiovascular outcomes in patients with systemic lupus erythematosus and lupus nephritis, Jorge and colleagues designed and emulated a pragmatic target trial. The researchers included patients diagnosed with SLE between March 2013 and August 2021 from a large U.S. multi-center electronic health record-based cohort of 96,511 individuals.
Among those, the researchers identified 426 patients who used SGLT2 inhibitors and 865 who used DPP4 inhibitors after SLE diagnosis. A subset included 154 and 270 patients with lupus nephritis in the SGLT2- and DPP4-inhibitor arms, respectively.
“We included all of the medications in those drug classes that are approved in the United States,” Jorge said.
The two groups were well-balanced in terms of baseline demographics. The mean age of the overall cohort was 57 years, while 89% percent were women, 36% were Black and 8% were Hispanic. Chronic kidney disease was reported in 35% of patients, while 24% had heart failure. Meanwhile, the use of Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers was reported in 45% of the cohort.
According to the researchers, SGLT2 inhibitor use was associated with a lower risk for major adverse cardiac events (MACE) (HR = 0.69; 95% CI, 0.48-0.99) and renal progression (HR = 0.71; 95% CI, 0.51-0.98), compared with DPP4 inhibition. In the lupus nephritis subgroup, SGLT2 inhibitor use also improved on MACE risk compared with DPP4 inhibitors (HR = 0.58; 95% CI, 0.34-0.99). Also in the lupus nephritis group, renal progression improved with SGLT2 inhibition compared with DPP4 inhibitors, but the difference failed to reach statistical significance, according to the findings.
Safety data demonstrated an elevated risk for genital infections in the SGLT2-inhibitor group.
“As expected, there was a higher risk for genital infections in SGLT2-treated patients,” Jorge said.
However, traumatic injury rates were comparable between the two treatment groups (HR = 1.02; 95% CI, 0.80-1.29), which the researchers noted was an “expected” outcome.
“We did not see an increased risk in overall severe infections in patients treated with SGLT2 inhibitors,” Jorge said.
“These findings indicate a potential role for SGLT2 inhibition to improve outcomes for patients with SLE and lupus nephritis and warrant further investigation in these populations,” she added.
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Jorge A. Abstract 1579. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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