Background/Purpose: Metformin is a mainstay of therapy for type 2 diabetes mellitus. Newer evidence suggests that metformin may reduce lupus flares. An entity called neutrophil extracellular traps (NETs) has been found to be important in the pathogenesis of lupus, as they promote plasmacytoid dendritic cells (PDCs) to differentiate and activate. These PDCs, when activated, release interferon α (IFNα), which plays a pivotal role in the pathogenesis of lupus. The formation of NETs is reactive oxygen species (ROS) dependent. Metformin can selectively inhibit mitochondrial respiratory chain complex I and decrease NADPH oxidase activity leading to a reduction in ROS production. A November 2015 article by Wang H, et al in Arthritis and Rheumatology designed a randomized, proof-of-concept trial to evaluate the efficacy and safety of metformin on a background of corticosteroids and conventional immunosuppressive agents in patients with mild or moderate lupus. That study demonstrated that add-on metformin reduced the risk of disease flares by 51% compared with conventional treatment only. Prednisone exposure was also lower in the metformin add-on group than in the conventional treatment group. The objective of our study is to compare the disease activity of lupus patients on metformin versus those not on metformin.

Methods: We conducted a retrospective review of lupus patients followed in our Rheumatology clinic over one year. The primary outcome was to determine if lupus patients on metformin had lower disease activity compared to those not taking metformin. The population for review included those from the Lupus Initiative. We compared the mean Systemic Lupus Erythematosus Activity Index (SLEDAI) scores which measures disease activity between the two groups.

Results: In total, 15 patients out of 1446 patients with lupus were taking metformin. Using a Wilcoxon rank sum test, there was a statistically significant difference in patients SLEDAI scores between the lupus patients taking metformin versus the lupus patients not taking metformin (SLEDAI z=-2.7, p= 0.0061). We found that the average SLEDAI score in those patients taking metformin was lower compared to those who were not on metformin. This is likely due to the mechanism of metformin which selectively inhibits mitochondrial respiratory chain complex I and decreases NADPH oxidase activity leading to decreased production of ROS. Reduced ROS production thus leads to fewer NETs forming, thus fewer PDCs differentiate and there is reduced release of IFNα which is a pivotal player in the pathogenesis of lupus. Further study comparing the mean prednisone dose between the two groups is currently underway.

Conclusion: We identified that lupus patients taking metformin had a lower median SLEDAI score compared to the patients not taking metformin. Metformin may play an important role in decreasing lupus flares by targeting NET activity and further research into this association should be done, as this may be one of the new approaches to treating lupus.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-impact-of-metformin-on-disease-activity-in-systemic-lupus-erythematosus/