GLP-1 receptor agonist exposure was associated with new-onset , especially with shorter exposure.
Evidence
This retrospective population-based case-control study compared 4,535 RA cases with 22,675 matched controls using a nationwide health provider database.
Caveat
The observational design cannot prove causality, and confounding by obesity, diabetes, indication, or exposure duration may explain part of the association.
Simplified
BACKGROUND: Obesity has been proposed as a risk factor for the development of (RA). (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.
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.
Key numbers
1.61
Liraglutide Exposure Odds Ratio
Odds ratio for cases with prior liraglutide exposure vs. controls.
1.69
Semaglutide Exposure Odds Ratio
Odds ratio for cases with prior semaglutide exposure vs. controls.
≤6 months
Shorter Exposure Association
Duration of GLP-1RA exposure associated with new-onset .
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