Comparative risk of rheumatoid arthritis between glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in type 2 diabetes

Oct 19, 2025Journal of autoimmunity

Risk of Rheumatoid Arthritis with Two Diabetes Drug Types: GLP-1 Receptor Agonists vs SGLT-2 Inhibitors in Type 2 Diabetes

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Abstract

In a cohort of 89,938 patients using GLP-1 receptor agonists, no significant difference in 7-year rheumatoid arthritis risk was observed compared to those using DPP-4 inhibitors.

GLP-1 receptor agonists showed a hazard ratio of 1.06 for RA risk compared to DPP-4 inhibitors, indicating no significant difference.
The hazard ratio for RA risk with GLP-1 receptor agonists compared to basal insulin was 0.98, also showing no significant difference.
SGLT2 inhibitors were associated with a lower risk of rheumatoid arthritis, with a hazard ratio of 0.88 compared to GLP-1 receptor agonists.
Cumulative incidence of RA was significantly lower in SGLT2 inhibitor users, as confirmed by Kaplan-Meier curves (log-rank p = 0.007).

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INTRODUCTION: Rheumatoid arthritis (RA) causes disability, chronic pain, and reduced quality of life. Preclinical studies suggest glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce inflammation and protect joint tissues. This study compared GLP-1 RAs with non-GLP-1 RAs on the risk of RA in patients with type 2 diabetes mellitus (T2DM).

METHODS: Using the TriNetX network (2016-2023), we identified 2,688,327 patients with T2DM. Propensity score matching yielded 89,938, 111,074, and 88,054 pairs of GLP-1 RA users versus dipeptidyl peptidase-4 inhibitors (DPP-4i), basal insulin, and sodium-glucose cotransporter-2 inhibitors (SGLT2i), respectively. Analyses followed an as-treated approach. Relative hazards of RA were estimated with Kaplan-Meier methods. Subgroup analyses were performed, and a sensitivity analysis used the intention-to-treat approach.

RESULTS: In matched cohorts, GLP-1 RAs showed no significant difference in 7-year RA risk versus DPP-4i (HR 1.06, 95 % CI 0.98-1.15) or basal insulin (HR 0.98, 95 % CI 0.89-1.08). By contrast, SGLT2i use was associated with lower RA risk compared with GLP-1 RAs (HR 0.88, 95 % CI 0.80-0.96). Kaplan-Meier curves confirmed a significantly lower cumulative incidence of RA in SGLT2i users (log-rank p = 0.007).

CONCLUSIONS: In this multicenter cohort study of patients with T2DM, GLP-1 RAs did not significantly alter RA risk compared with DPP-4i or basal insulin. In contrast, SGLT2i was associated with a significantly reduced risk of new-onset RA, suggesting potential anti-inflammatory benefits.

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Comparative risk of rheumatoid arthritis between glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in type 2 diabetes

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