The association between glucagon-like peptide-1 receptor agonist and rheumatoid arthritis: a population-based case-control study.

Therapeutic advances in musculoskeletal disease2026PMID: 41773280

View on PubMed DOI: 10.1177/1759720X261425441

Plain Language Summary

Retrospective population-based case-control study investigating whether GLP-1 RA use is associated with reduced risk of new-onset rheumatoid arthritis (RA). Motivated by GLP-1 RA immunomodulatory effects and obesity as an established RA risk factor, the study examines whether semaglutide's anti-inflammatory properties reduce RA incidence. Provides the first population-scale epidemiological data on GLP-1 RA use and RA onset—contributing to the expanding literature on GLP-1 RA effects on autoimmune disease outcomes beyond their primary metabolic indications.

Abstract

BACKGROUND: Obesity has been proposed as a risk factor for the development of rheumatoid arthritis (RA). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for weight reduction and glycemic control and have been shown to exert immunomodulatory effects. However, the association between GLP-1RA use and the onset of RA remains unclear. OBJECTIVES: To investigate the association between GLP-1RA exposure and new-onset RA in a large population-based study. DESIGN: Retrospective, population-based case-control study. METHODS: We analyzed data from a nationwide health provider database. All adults diagnosed with RA were matched with controls (1:5) by age, sex, and socioeconomic status. The primary exposure was GLP-1RA use within the 10 years preceding RA diagnosis. Multivariable logistic regression models were used to estimate the association between GLP-1RA use and new onset RA, adjusting for age, body mass index (BMI), smoking status, and diabetes mellitus (DM). Duration of GLP-1RA exposure was stratified according to length of exposure (⩽6 vs >6 months). RESULTS: The study included 4535 RA cases and 22,675 matched controls. In univariate analyses, subcutaneous semaglutide and liraglutide were significantly associated with new onset RA, while dulaglutide showed a non-significant trend. These associations remained significant in multivariable models adjusted for potential confounders. Higher BMI categories and DM were independently associated with new onset RA. When GLP-1RA exposure was stratified according to length of exposure (⩽6 vs > 6 months), shorter exposure, but not longer exposure, was associated with new onset RA. CONCLUSION: GLP-1RA use was associated with new onset RA. However, prolonged treatment appeared to attenuate this association, potentially reflecting the beneficial effects of GLP-1RAs on BMI and glycemic control, which are independently associated with new onset RA.

Authors

Israel, Ariel; Hassan, Fadi; Merzon, Eugene; Kurtam, Jalal; Awad, Jamal; Assalia, Mai; Green, Ilan; Vinker, Shlomo; Naffaa, Mohammad E

Keywords

glucagon-like peptide-1 receptor agonistsimmunomodulationobesityrheumatoid arthritis