#3-04E. SGLT2 Inhibitors and Autoimmune Prevention: A Surprise Finding (Arthritis Rheumatol, 2025)

As the use of GLP-1 receptor agonists and SGLT2 inhibitors expands rapidly beyond diabetes management, a critical question arises for clinicians: do the known immunomodulatory effects of these drugs influence the onset of autoimmune diseases? A recent population-based cohort study involving over 229,000 adults with type 2 diabetes addressed this by comparing the incidence of autoimmune rheumatic diseases (ARDs) following the initiation of GLP-1RAs or SGLT2 inhibitors versus DPP4 inhibitors. The results offered reassuring safety data, demonstrating that neither drug class was associated with an increased risk of overall ARDs. However, a striking and potentially practice-changing signal emerged: the use of SGLT2 inhibitors was associated with a 49% reduction in the risk of developing systemic ARDs (SARDs), such as systemic lupus erythematosus and systemic sclerosis. While this points to a novel preventative benefit, critical appraisal is essential; the study's mean follow-up of approximately 1.5 years may be insufficient to fully capture diseases with long preclinical phases like rheumatoid arthritis. Nevertheless, for physicians, this study not only confirms the autoimmune safety of these metabolic therapies but also highlights a promising avenue for SGLT2 inhibitors in the prevention of rare systemic autoimmune conditions.

Citation: Karacabeyli D, Lacaille D, Lu N, Xie H, Aviña-Zubieta JA. Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Risk of Autoimmune Rheumatic Diseases. Arthritis & Rheumatology. 2025.

DOI: 10.1002/art.70044

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