GLP-1 Receptor Agonists Show Lower Risk for MACE and VTE in Lupus and Type 2 Diabetes Patients Compared to DPP4 Inhibitors

Patients with systemic lupus erythematosus (SLE) and type 2 diabetes who are treated with glucagon-like peptide-1 (GLP-1) receptor agonists exhibit a reduced risk for major adverse cardiac events (MACE), venous thromboembolism (VTE), progression of kidney disease, and all-cause mortality compared to those treated with dipeptidyl peptidase 4 (DPP4) inhibitors. This finding was presented by April Jorge, MD, a rheumatologist at Massachusetts General Hospital and instructor in medicine at Harvard Medical School, at ACR Convergence 2024.

The study utilized electronic health records from the TriNetX database to emulate a target trial, comparing the effects of GLP-1 receptor agonists and DPP4 inhibitors in patients with SLE or lupus nephritis and type 2 diabetes. The analysis included 910 patients initiating GLP-1 receptor agonists and 1,004 starting DPP4 inhibitors, with a significant proportion having lupus nephritis.

Results from the per-protocol analysis showed that GLP-1 receptor agonist users had significantly lower risks for MACE (HR = 0.66), VTE (HR = 0.49), kidney disease progression (HR = 0.77), and all-cause death (HR = 0.26) compared to DPP4 inhibitor users. Similar benefits were observed in the intention-to-treat analysis, with GLP-1 receptor agonist users experiencing lower risks for MACE (HR = 0.8), kidney disease progression (HR = 0.79), and all-cause death (HR = 0.42).

Among patients with lupus nephritis, the use of GLP-1 receptor agonists was associated with fewer major adverse cardiac events (HR = 0.64) and less kidney disease progression (HR = 0.7) compared to DPP4 inhibitors in the per-protocol analysis.

Dr. Jorge emphasized the potential cardioprotective and nephroprotective benefits of GLP-1 receptor agonists in patients with lupus and lupus nephritis, similar to those observed in other populations such as those with obesity and diabetes. She called for further mechanistic studies and prospective research to better understand the benefits of GLP-1 receptor agonists in patients with lupus and other rheumatic diseases, including their potential impact on disease activity through anti-inflammatory effects.