Patients with lupus, type 2 diabetes at lower risk for MACE, VTE with GLP-1 vs DPP4 drugs
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WASHINGTON — Patients with lupus and type 2 diabetes who receive glucagon-like peptide-1 receptor agonists demonstrate a lower risk for cardiac events and kidney disease progression vs. dipeptidyl peptidase 4 inhibitors, according to data.
“The risks for cardiovascular disease are thought to be at least double for people with lupus, but this is even higher in young women with lupus compared with their healthy peers,” April Jorge, MD, a rheumatologist at Massachusetts General Hospital and instructor in medicine at Harvard Medical School, told attendees at ACR Convergence 2024. “We know the risk for progressing to end-stage kidney disease for patients with lupus nephritis can be as high as 10% to 30%, so there’s clearly a major unmet need for new treatments and approaches.
“There’s a lot of interest in the use of medications like the glucagon-like peptide 1, or GLP-1, receptor agonists, because these medications have multiple different mechanisms of benefit and different effects that lead to cardioprotective and nephroprotective benefits, at least in other disease populations,” she added.
To compare the cardiac and renal impacts of GLP-1 receptor agonists vs. other oral hypoglycemic agents — specifically dipeptidyl peptidase 4 (DPP4) inhibitors — for patients with systemic lupus erythematosus or lupus nephritis, Jorge and colleagues emulated a target trial using electronic health records from the TriNetX database.
“This is an approach to try to use observational data to try to answer a causal question that a randomized controlled trial would ideally answer, but is not feasible or practical at that time,” Jorge said. “The way you do this is, you specify. If there was a hypothetical randomized controlled trial to answer the question, what would be all the components of the trial protocol, and can you emulate that as best as possible using observational data to try to reduce potential confounding?”
In addition to SLE, study participants also had type 2 diabetes, so that a GLP-1 receptor agonist or DPP4 inhibitor was indicated. The study included 910 patients who initiated GLP-1 receptor agonists, including 267 with lupus nephritis, and 1,004 who started DPP4 inhibitors — 324 with lupus nephritis. Their mean age was 55 years, 92% were women, and a third had chronic kidney disease of stage 3 or higher.
In a per-protocol analysis, Cox regression showed that GLP-1 receptor agonist users had lower risks for major adverse cardiac events (HR = 0.66; 95% CI, 0.48-0.91), venous thromboembolism (HR = 0.49; 95% CI, 0.24-0.97), kidney disease progression (HR = 0.77; 95% CI, 0.6-0.98) and all-cause death (HR = 0.26; 95% CI, 0.1-0.68), compared with patients taking DPP4 inhibitors, according to the researchers.
Intention-to-treat analysis similarly showed lower risks for major adverse cardiac events (HR = 0.8; 95% CI, 0.62-1.03), kidney disease progression (HR = 0.79; 95% CI, 0.65-0.96), and all-cause death (HR = 0.42; 95% CI, 0.25-0.73) among GLP-1 receptor agonist users.
Among patients with lupus nephritis, GLP-1 agonist use was associated with fewer major adverse cardiac events (HR = 0.64; 95% CI, 0.41-0.98) and less kidney disease progression (HR = 0.7; 95% CI, 0.49-1), compared with DPP4 inhibitors in per-protocol analysis.
“I think these are really interesting findings that suggest there might be similar cardioprotective and nephroprotective benefits in patients with lupus and lupus nephritis as have been seen in other populations like obesity and diabetes,” Jorge said. “These findings really indicate a potential role for this medication that warrants further investigation, and I think that we need to do mechanistic studies to better understand the potential benefit of GLP-1 receptor agonists in patients with lupus and other rheumatic diseases, as well.
“Ideally, we would have prospective studies with these patients, and we can really try to isolate the effect in patients with lupus and also understand if there might be an impact on disease activity through the anti-inflammatory effects of these medications, rather than just the cardioprotective and nephroprotective benefits,” she added.
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Jorge A. Abstract #2576. Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
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