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. 2022 Jul 27:9:934184.
doi: 10.3389/fmed.2022.934184. eCollection 2022.

Sulfonylureas or biguanides is associated with a lower risk of rheumatoid arthritis in patients with diabetes: A nationwide cohort study

Yu-Jih Su  1   2 , Jing-Yang Huang  3   4 , Cong-Qiu Chu  5 , James Cheng-Chung Wei  6   7   8
Affiliations

Sulfonylureas or biguanides is associated with a lower risk of rheumatoid arthritis in patients with diabetes: A nationwide cohort study

Yu-Jih Su et al. Front Med (Lausanne). .

Abstract

Objective: Diabetes mellitus (DM) is associated with immune dysregulation, while sulfonylureas or biguanides have been linked to anti-inflammatory mechanisms. In this study, we aimed to examine the occurrence rate of rheumatoid arthritis (RA) among DM patients and its incidence rate between different treatments.

Methods: This cohort study used the Taiwan National Health Insurance Research Database between 1997 and 2013 to evaluate the primary outcomes of the preventive role of sulfonylureas or biguanides in the development of RA. We used the Chi-square test for categorical variables and Cox proportional hazard regression and log-rank test to explore the time for development of RA in DM patients. Logistic regression was adopted to estimate the odds ratio of RA in different dosages of medication exposure.

Results: Our cohort study included 94,141 DM cases. The risk of RA development of non-sulfonylureas/biguanides users among the DM group in each analysis was set as the reference, and the adjusted hazard ratio of RA in DM patients who were using sulfonylureas or biguanides was 0.73 (95% confidence interval 0.60-0.90). Within 1 year before the index date, compared with no-biguanides users, patients with more than 180 days of prescription of biguanides had a significantly lower RA risk. Similarly, the significantly lower risk of RA was still observed in DM patients who had more than 365 days of prescription of sulfonylurea within 2 or 3 years before the index date of first RA visit (all p < 0.05).

Conclusion: Our data suggest that sulfonylureas or biguanides are associated with a lower rate of RA development in patients with DM; the effect of biguanides appeared more rapid than that of sulfonylureas, but the sulfonylureas might have a longer effect on lowering RA development incidence.

Keywords: biguanides; diabetes; incidence rate; rheumatoid arthritis; sulfonylureas.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The flowchart of study design. There were 132,369 patients with diabetes in our cohort. We had excluded 33,951 patients for missing data, 673 patients with age <18 years, 2,025 patients with previous RA diagnosis, 2,025 patients with type 1 diabetes, and 1,423 patients with missing age or gender data. So, there were 94,141 diabetes patients enrolled in our cohort. According to the comorbidities, 494 patients were diagnosed with RA, and 93,647 patients were not diagnosed with RA. We had further matched age and gender between the RA patients and non-RA patients. Finally, there were 494 RA patients and 988 non-RA patients in our nested case-control study. The comparisons between the two subgroups in the nested case-control analysis were used to demonstrate the cumulative doses of anti-diabetes treatment and their relation to RA incidence rate.
Figure 2
Figure 2
Kaplan-Meier curves of cumulative rheumatoid arthritis incidence proportion in diabetes patients by oral anti-glycemic agent. Kaplan-Meier curves of cumulative rheumatoid arthritis incidence proportion in diabetes patients by the use of either biguanides (A) or sulfonylureas (B). Either biguanides users or sulfonylureas users had lower cumulative rheumatoid arthritis incidence rates (p = 0.0061 for biguanides users and p = 0.0009 for sulfonylureas users).
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