Anne Arundel Medical Center Washington DC, District of Columbia, United States
Disclosure(s): No financial relationships with ineligible companies to disclose
Background/Purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by T- and B-cell activation and pro-inflammatory cytokines such as TNF-α and IL-6 and is managed by disease-modifying antirheumatic drugs (DMARDs) [1]. SGLT2 inhibitors and GLP-1 receptor agonists, developed for type 2 diabetes, have shown cardiovascular, renal, and potential anti-inflammatory benefits via reduced cytokine production and macrophage activation [2-5]. Clinical data on their effect in RA is limited. This study examines the association between SGLT2 or GLP-1 use and RA flare outcomes in DMARD-treated patients using real-world retrospective data. Methods: A retrospective cohort study was conducted using TriNetX data between 2019 and 2024. Adults with RA and >12 months follow-up after DMARD initiation were included and categorized into: (1) DMARDs only, (2) DMARDs + SGLT2 inhibitor, and (3) DMARDs + GLP-1 receptor agonist. Patients with other inflammatory arthritides, malignancy, transplant, pregnancy, combined SGLT2/GLP-1 use, or prolonged prednisone use ( >3 months) were excluded. Data included demographics, comorbidities, treatment timing, short-term oral prednisone, IV methylprednisolone, joint injections, ESR/CRP, and DMARD changes. RA flares were defined using a composite of: IV methylprednisolone, intra-articular injection, oral prednisone use less than 3 months, number of DMARD escalation, or increased CRP (≥10 mg/L) or ESR (≥20 mm/h). Results: In Table 1, the GLP-1 group had the highest baseline DMARD count (mean 2.51), lowest end count (mean 1.31). ESR and CRP were most elevated in the SGLT2i group. Table 2 reports significantly different flare burden scores (p = 0.00006): DMARDs-only (1.12 ± 2.44), DMARDs+GLP-1 (1.71 ± 3.79), and DMARDs+SGLT2i (1.30 ± 1.78). Flare proxies such as IV steroids, joint injections, and inflammatory marker elevations were more common in the GLP-1 group. The composite flare burden score included oral prednisone use (1 point if present), IV methylprednisolone and joint injections (1 point per three administrations), frequency of CRP ≥10 mg/L, frequency of ESR ≥20 mm/hr, and if DMARD escalation was present. Flare proxies like IV steroids, injections, and inflammatory marker elevations were more frequent in the GLP-1 group. These findings suggest a possible association between GLP-1 use and higher flare burden, though further adjustment for baseline differences is needed. Table 3 shows patients with post-initiation flare declined significantly in the SGLT2i group (34.1% to 12.0%, p = 0.0407) and non-significantly in the GLP-1 group (41.0% to 20.7%, p = 0.1525). Limitations include lack of standardized disease activity measures (e.g., DAS28), potential confounding factors, and the inability to include DMARD escalation in pre-treatment and post-treatment analysis. Conclusion: The use of SGLT2i was associated with a significant reduction in RA flares. GLP-1 showed a non-significant trend toward flare reduction, though this may reflect higher baseline RA severity which may influence the trend. These findings support the need for further p<strong id="docs-internal-guid-f74d5414-7fff-921e-06e4-f93c3523c955" style="font-style: normal; font-variant-caps: normal; letter-spacing: normal; orphans: auto; text-align: start; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px; -webkit-text-stroke-width: 0px; text-decoration: none; caret-color: #000000; color: #000000; font-weight: normal;">rospective studies to validate the anti-inflammatory potential of SGLT2 inhibitors in RA and further explore the effect of GLP-1 on RA flare.
