Adherence to metformin and the onset of rheumatoid arthritis: a population-based cohort study

M. E. Naffaa, V. Rosenberg, A. Watad, S. Tiosano, Y. Yavne, G. Chodick, H. Amital, V. Shalev

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20 Scopus citations


Objective: The aim of this retrospective cohort study was to examine whether adherence to metformin treatment may be associated with lower onset of rheumatoid arthritis (RA). Method: Using the computerized databases of a 2.3-million state-mandated health services organization in Israel, we identified incident RA cases among a cohort of 113 749 adult patients who initiated metformin therapy between 1998 and 2014. Adherence was assessed by calculating the mean proportion of follow-up days covered (PDC) with metformin. Results: During the 18 year study period, there were 558 incident RA cases (61 per 100 000 person-years). Adherence to metformin treatment was associated with a lower risk of developing RA, with the lowest risk recorded among patients with a PDC of 40–59% [adjusted hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.45–0.84] compared with non-adherent patients (PDC < 20%). A mean daily metformin dose of 2550 mg or more was also associated with a lower risk of developing RA (adjusted HR 0.62, 95% CI 0.46–0.84) compared to a daily dose of 850 mg or less. In stratified analyses by gender, the negative association between adherence and the risk of RA was limited to women alone. Conclusions: Adherence to metformin treatment is associated with a reduced risk of developing RA in women. Further studies are needed to assess the effect of metformin on RA development in other patient populations.

Original languageEnglish
Pages (from-to)173-180
Number of pages8
JournalScandinavian Journal of Rheumatology
Issue number3
StatePublished - 3 May 2020
Externally publishedYes

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© 2020, © 2020 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation.


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