ArticleFrontiers in immunology2026
The association between SGLT2 inhibitors and rheumatoid arthritis risk in type 2 diabetes: findings from large-scale emulated target trials.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Findings Interpretation Concerns Regarding the Emulated Target Trial of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Psoriatic Arthritis [Response to Letter].Drug design, development and therapy · 2026Article
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6 authors.
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Abstract
Introduction: Globally, the prevalence of rheumatoid arthritis (RA) is on the rise. Certain antidiabetic medications have been reported to lower the risk of RA. In this study, we conducted multicenter emulated target trials to compare the risk of RA development between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and non-SGLT2i treatment options in patients with type 2 diabetes mellitus (T2DM). Methods: We identified 4,991,988 patients with T2DM from the TriNetX network between January 1, 2016, to June 30, 2023. From this cohort, we selected 310,507, 206,069, and 80,846 propensity score-matched pairs of patients using SGLT2i versus sulfonylureas, dipeptidyl peptidase-4 inhibitors (DPP-4i), and pioglitazone, respectively. The Kaplan-Meier method was used to determine the relative hazards of developing RA among these groups. Subgroup analyses were conducted based on sex, age, race, obesity status, HbA1C levels, and eGFR, with an additional sensitivity analysis using the intention-to-treat approach. Results: SGLT2i use was associated with a significantly lower risk of incident RA compared to sulfonylurea use (HR: 0.899, 95% CI: 0.835-0.968). However, there was no significant difference in RA risk when comparing SGLT2i with DPP-4 inhibitors (HR: 0.914, 95% CI: 0.831-1.005) or pioglitazone (HR: 0.922, 95% CI: 0.796-1.068). Kaplan-Meier curves demonstrated that SGLT2i users had a significantly lower likelihood of developing RA than sulfonylurea users (log-rank p = 0.004). Subgroup analyses further indicated that SGLT2i use was consistently associated with a lower risk of RA across all analyzed patient subgroups compared to sulfonylureas. Additionally, sensitivity analyses confirmed the robustness of these findings, aligning with the results from the emulated target trial comparing SGLT2i to sulfonylureas. Discussion: This study found that SGLT2i use was associated with a lower risk of incident RA compared with sulfonylurea use among patients with T2DM. However, because of the observational study design, these findings should be interpreted as associations rather than evidence of causality.
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