Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory disease, characterized by persistent inflammation of the synovium and joint destruction, which leads to symmetrical polyarthritis accompanied by joint swelling, pain, and stiffness [1]. Without appropriate treatment, RA can result in musculoskeletal impairment, long-term disability, and premature death [2,3]. In 2020, it was estimated that approximately 17.6 million people worldwide had RA, with a global age-standardized prevalence rate of 209 cases per 100,000 population (0.21 %), marking a 14.1 % increase since 1990 [3]. RA prevalence in the United States is estimated at 0.5 %–1 %, affecting over 1.3 million adults [4].

RA is more common in women and tends to occur more frequently in older individuals, particularly those between the ages of 60 and 70, which aligns with the typical age of onset for type 2 diabetes mellitus (T2DM) [3,5]. The high levels of systemic inflammation in RA can lead to extra-articular manifestations, including pulmonary involvement, vasculitis, and systemic comorbidities such as T2DM [[6], [7], [8]]. Because both RA and T2DM share a common pathogenesis of systemic inflammation, the latter has been linked to an increased risk of RA [7,9]. A meta-analysis of four retrospective cohorts demonstrated a 28 % lower risk of RA among dipeptidyl peptidase-4 inhibitors (DPP-4i) users [10]. In a population-based study using U.S. insurance claims data, Kim et al. showed the risk of incident RA was lower in the DPP-4i group [11]. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) mimic the actions of endogenous GLP-1 by activating GLP-1 receptors, which results in increased insulin secretion, slow gastric emptying, reduced food intake, and significant weight reduction [12]. Additionally, GLP-1 receptors are expressed on macrophages and fibroblast-like synoviocytes in the synovium [13]. In fibroblast-like synoviocytes from RA patients, lixisenatide administration has been shown to reduce the inflammatory response by decreasing the expression of pro-inflammatory cytokines [14]. The administration of lixisenatide in RA patients has been shown to not only reduce inflammation but also inhibit matrix metalloproteinase (MMP) activity, a key player in tissue destruction, making it a promising therapeutic candidate for RA management [15]. In recent years, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have also been increasingly recognized for their potent anti-inflammatory effects [16].

Despite these findings, large-scale evidence on the potential repurposing effects of GLP-1 RAs, DPP-4i, and SGLT2i on RA risk remains limited. Moreover, GLP-1 RAs and basal insulin are often considered comparable treatment options for patients with poorly controlled hyperglycemia [17]. Therefore, we designed this study to evaluate the potential effects of GLP-1 RAs, DPP-4 inhibitors, basal insulin, and SGLT2 inhibitors on the risk of RA development in patients with T2DM.