Glucagon‐Like Peptide 1 Receptor Agonists, Sodium‐Glucose Cotransporter 2 Inhibitors, and Risk of Autoimmune Rheumatic Diseases

OBJECTIVE: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) facilitate weight loss and exhibit immunomodulatory effects, but their impact on the risk of developing autoimmune rheumatic diseases (ARDs) is unclear. We compared ARD incidence following initiation of GLP-1RAs or SGLT2i versus a weight-neutral comparator (dipeptidyl peptidase 4 inhibitors [DPP4i]). METHODS: We performed a population-based cohort study using administrative health data from a Canadian province with universal health care. We included adults with type 2 diabetes (T2D) and no prior ARD initiating a GLP-1RA, SGLT2i, or DPP4i between January 1, 2014, and December 31, 2022. Incident ARD cases, including rheumatoid arthritis, psoriatic disease, axial spondyloarthritis, and systemic ARDs (SARDs; systemic lupus erythematosus, systemic sclerosis, Sjögren disease, idiopathic inflammatory myopathies, and systemic vasculitides), were identified using validated algorithms. Propensity score (PS) weighting was used to balance cohorts at treatment initiation. Then hazard ratios (HRs) were estimated using Cox regression. RESULTS: Among 229,300 adults, 49,514 initiated GLP-1RAs, 101,925 initiated SGLT2i, and 77,861 initiated DPP4i. After PS weighting, ARD incidence per 10,000 person-years was 29.1 (95% confidence interval [CI] 23.5-35.5) with GLP-1RAs, 24.4 (95% CI 19.8-29.7) with SGLT2i, and 27.3 (95% CI 22.1-33.4) with DPP4i. Mean follow-up was 1.3 to 1.6 years. Relative to DPP4i, adjusted HRs (aHRs) of ARD were 1.04 (95% CI 0.81-1.33) with GLP-1RAs and 0.93 (95% CI 0.75-1.16) with SGLT2i. Risk of SARDs, but not other diseases, was lower with SGLT2i versus DPP4i (aHR 0.51 [95% CI 0.31-0.84]). CONCLUSION: Neither GLP-1RA nor SGLT2i treatment was associated with increased or decreased ARD risk versus DPP4i in adults with T2D; however, SGLT2i use was associated with significantly lower risk of SARDs, warranting further study.