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, 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.

Keywords: autoantibodies; lupus erythematosus; systemic; therapeutics.

Conflict of interest statement

Competing interests: SY reports personal grants from Shanghai Shenkang Promoting Project (16CR1013A); LL reports grants from the National Key Research and Development Program of China (2017YFC0909002); LM reports a grant from the National Institutes of Health (R01 AI128901).

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Outcome measures of pooled analysis. (A) Flares, changes of prednisone and body mass index (BMI) during 12-month follow-up. (B) Kaplan-Meier curves of flare-free survival and major flare-free survival. P values and HRs were adjusted for trial using Cox model.
Figure 2
Figure 2
Subgroup and interaction analysis. (A) Forest map for different subgroups. Comparisons of flare-free survival curves in patients with or without concomitant use of hydroxychloroquine (HCQ) (B), with disease duration

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