Effects of metformin on disease flares in patients with systemic lupus erythematosus: post hoc analyses from two randomised trials
Fangfang Sun, Shikai Geng, Haiting Wang, Huijing Wang, Zhe Liu, Xiaodong Wang, Ting Li, Weiguo Wan, Liangjing Lu, Xiangyu Teng, Laurence Morel, Shuang Ye
Abstract
OBJECTIVE: To confirm that metformin prevents flares in patients with SLE with low disease activity, we performed a post hoc analysis combining our previous two randomised trials. METHODS: Post hoc analyses were performed on data from the open-labelled proof-of-concept trial (n=113, ChiCTR-TRC-12002419) and placebo-controlled 'Met Lupus' trial (n=140, NCT02741960) comparing the efficacy of metformin versus placebo/nil add-on to standard therapy in patients with SLE with low disease activity (SELENA-SLEDAI ≤4). The primary endpoint was defined by the SELENA-SLEDAI Flare Index at 12-month follow-up. A subgroup analysis was performed. RESULTS: Overall, 201 eligible patients were included, with 99 allocated to metformin group and 102 allocated to the placebo/nil group. By 12 months of follow-up, 21 patients (21.2%) flared in the metformin group, as compared with 36 (35.3%) in the placebo/nil group (p=0.027, risk ratio=0.68, 95% CI 0.46 to 0.96). Subgroup analysis showed that patients with negative anti-dsDNA antibody and normal complement at baseline, and a disease duration <5 years with concomitant use of hydroxychloroquine had a better response to metformin. CONCLUSION: Post hoc pooled analyses suggested that metformin reduced subsequent disease flares in patients with SLE with low disease activity, especially for serologically quiescent patients.