The relationship between insulin resistance and the use of disease modifying anti-rheumatic drugs and biological agents in patients with rheumatoid arthritis

ABSTRACT GÜL ESEN, R. (2025) .The Relationship Between Insulin Resistance and the Use of Disease-Modifying Anti-Rheumatic Drugs and Biological Agents in Patients with Rheumatoid Arthritis. Van Yüzüncü Yıl University Faculty of Medicine, Department of Physical Medicine and Rehabilitation. Medical Specialty Thesis. Van. Introduction and Objective: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by symmetrical joint involvement and is influenced by environmental, genetic, and immunological factors. Extra-articular manifestations can also be observed in many systems. It typically presents in the 40s to 50s and is seen three times more frequently in women than men. In chronic systemic inflammatory diseases such as RA, cytokines like interleukins and TNF-alpha, which are secreted during inflammation, have been shown in many studies to increase insulin resistance. There are also studies suggesting that certain anti-inflammatory drugs used in RA treatment, particularly biological agents, may have a beneficial effect on insulin resistance. In our study, we aimed to compare the effects of anti-TNF and JAK inhibitors, which are biological agents used in the treatment of RA, on insulin resistance with conventional synthetic DMARD therapy. Materials and Methods: This study was conducted with 80 patients diagnosed with Rheumatoid Arthritis aged between 18-85 years who applied to the Rheumatology Outpatient Clinic of the Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Van Yüzüncü Yıl University between September 2023 and September 2024. Patients were divided into two groups: 32 using conventional synthetic DMARDs (csDMARDs) and 35 using biological agents. Fasting blood glucose and insulin levels were measured at baseline and at the 12th-week follow-up; DAS-28 and HOMA-IR values were calculated. Both groups were evaluated comparatively. The biological agent group was further divided into two subgroups (anti-TNF and JAK inhibitors) and analyzed accordingly. Results: No statistically significant differences were found between Group A (biological agents) and Group B (csDMARDs) in terms of mean age and gender, which was consistent with the literature. In our study, since we worked with patients under controlled follow-up, no relationship was found between DAS28 and HOMA-IR values in either group (p>0.05). The changes in fasting blood glucose, insulin, and HOMA-IR values between the two check-ups were not significant for the csDMARD group (p>0.05). However, in the biological agent group, all three variables showed a significant decrease at the second check-up compared to the first and compared to the csDMARD group (p<0.05). Additionally, the mean HOMA-IR values were >2.5 for the csDMARD group and <2.5 for the biological agent group at both time points. The biological agent group was further divided into two subgroups (anti-TNF and JAK inhibitors), and differences between these were analyzed. While there was no significant difference in mean DAS28 scores, a significant decrease was observed in the JAK inhibitor group compared to the anti-TNF group. No significant difference was observed in fasting blood glucose levels. However, a significant decrease in insulin and HOMA-IR values was observed at the 12-week follow-up in the anti-TNF group, while no significant change was detected in the JAK inhibitor group. Conclusion: In this study investigating the relationship between insulin resistance and the use of anti-inflammatory drugs, particularly csDMARDs and biological agents (anti-TNF and JAK inhibitors), in an autoimmune and inflammatory rheumatologic disease like RA, we found that patients using csDMARDs were more prone to insulin resistance, while biological treatment, especially with anti-TNF agents, significantly reduced insulin resistance. Keywords: Rheumatoid arthritis, insulin, glucose, insulin resistance, HOMA-IR, csDMARD, Anti-TNF-alpha therapy, JAK-inhibitor therapy.