Researchers highlight that the observed benefits may extend beyond glucose control and weight management, suggesting broader protective effects of GLP-1RA in this population.
The study, led by Dr. April Jorge from the Division of Rheumatology, Allergy, and Immunology at Massachusetts General Hospital, aimed to assess whether GLP-1RA use could improve cardiovascular and kidney outcomes in patients with
systemic lupus erythematosus (SLE) and lupus nephritis (LN). GLP-1RAs are already known for their cardioprotective and kidney-protective effects in type 2 diabetes, but their potential impact in patients with autoimmune conditions has not been well characterized.
To investigate this, the research team conducted a pragmatic target trial using a large multi-center electronic health record database from the United States. They compared GLP-1RA users with patients treated with DPP-4 inhibitors, employing propensity score overlap weighting to emulate randomization and balance baseline characteristics between the two groups. The outcomes analyzed included major adverse cardiovascular events (MACE), venous thromboembolism (VTE), kidney disease progression—defined as a decline in eGFR by ≥30% or new-onset end-stage kidney disease—and all-cause mortality. A secondary analysis focused specifically on patients with LN.
The study included 910 patients initiating GLP-1RA therapy and 1,004 starting DPP-4 inhibitors, with 267 and 324 patients with LN in each group, respectively.
After statistical adjustments, the results showed that GLP-1RA use was associated with lower risks across all measured outcomes. Specifically, the risk of MACE decreased by 34% (HR 0.66, 95% CI 0.48-0.91), VTE by 51% (HR 0.49, 95% CI 0.24-0.97), kidney disease progression by 23% (HR 0.77, 95% CI 0.60-0.98), and all-cause mortality by 74% (HR 0.26, 95% CI 0.10-0.68) compared with DPP-4 inhibitors. Among patients with LN, GLP-1RA therapy was similarly linked with reduced risks of MACE and kidney disease progression.
Key Points:
- GLP-1RA use was linked to lower risks of MACE, VTE, kidney disease progression, and all-cause mortality in patients with SLE and T2D.
- Similar benefits were observed among patients with lupus nephritis.
- The protective effects of GLP-1RA may extend beyond weight loss and glucose control.
- Study supports considering GLP-1RA as a treatment strategy to reduce cardiovascular and kidney complications in lupus patients.
The findings suggest that GLP-1RA may offer meaningful protective effects for patients with lupus and type 2 diabetes, including those with kidney involvement. By reducing the risk of major cardiovascular events, venous thrombosis, kidney decline, and overall mortality, GLP-1RA could provide a valuable treatment strategy beyond conventional glycemic and weight management.
The study highlights the potential of GLP-1RA as a therapeutic option in complex populations where traditional interventions may not fully address cardiovascular and renal risk. Further research is encouraged to validate these findings and explore the mechanisms behind the observed benefits, potentially shaping future guidelines for the management of lupus patients with type 2 diabetes.
Reference:
Jorge, A., Patel, A. V., Zhou, B., Zhang, L., & Choi, H. Glucagon-Like Peptide-1 Receptor Agonist Use and the Risk of Adverse Cardiac and Kidney Outcomes Among Patients with Systemic Lupus Erythematosus and Lupus Nephritis. Arthritis & Rheumatology. https://doi.org/10.1002/art.43403
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