Abstract: Objective · To evaluate the efficacy and safety of a long-term adding metformin to a basic treatment strategy in systemic lupus erythematosus (SLE), and analyze whether the beneficial effects of metformin add-on treatment during the open-label proof-of-concept trial persisted during a posttrial follow-up (the metabolic memory effect), as there is a paucity of systematically collected data concerning long-term metformin in SLE. Methods ·Subjects who had participated in the open-label proof-of-concept trial and gave informed consent to this study were enrolled, and the disease flares and long-term adverse effects between metformin group and control group were compared. In addition, whether the benefit regarding decreased disease flare persisted after metformin withdrawal during the post-trial follow-up was investigated. Results · Twenty-nine subjects in the former metformin add-on strategy group and 28 subjects in the former control group were enrolled. No adverse reactions of metformin occurred during the study. The risk of disease flare in the control group was higher than that in the continuous metformin group, but the difference was not statistically significant (P0.326). After metformin withdrawal, the risk of disease flare in the metformin group gradually increased to the control group (P0.998). There was no significant difference between the two continuous metformin groups whose metformin using duration are 2.56 years and 5.00 years respectively (P0.802). Conclusion · A long-term metformin add-on treatment is security, and can keep SLE patients in a lower risk of disease flare. The metabolic regulation of metformin in SLE immune disorder may present a time-dependent metabolic memory effect.

Key words: systemic lupus erythematosus, metformin, metabolism and immune, post-trial follow-up, metabolic memory effect