The Effect of Metformin on Reducing Lupus Flares

A Multicenter, Randomised, Double-blind Placebo Controlled Trial on the Efficacy and Safety of add-on Metformin to Conventional Immunosuppressants in Systemic Lupus Erythematosus

This is a multicenter, randomised, double-blind placebo controlled trial on the efficacy and safety of add-on metformin to conventional immunosuppressants in systemic lupus erythematosus (SLE).

The purpose of this study is to evaluate: 1) the effect of metformin on reducing disease flares; 2) the influence of metformin on corticosteroid sparing effect; 3) the influence of metformin on body mass index (BMI); 4) the safety of metformin.

Inclusion Criteria:

• Willingness of the subject to participate in the study, proven by signing the informed consent;
• Systemic lupus erythematosus (SLE), as defined by meeting at least 4 of 11 classification criteria of American College of Rheumatology for the classification of systemic lupus erythematosus, either sequentially or coincidentally. The 4 criteria doesn't need to be present at the time of study enrollment;
• The course of SLE longer than1 year; and there is a clear record of disease flares in the past 1 year with prednisone more than 20mg/day;
• Patients with mild/moderate disease activity (score≤ 6 at screening on SLEDAI); no British Isles Lupus Assessment Group (BILAG) A or no more than one B;
• A stable treatment regimen with fixed doses of prednisone (≤ 20mg/day), antimalarial, or immunosuppressive drugs (azathioprine/ mycophenolate mofetil/ methotrexate/ ciclosporin/ leflunomide/ thalidomide) for at least 30 days.

Exclusion Criteria:

• Patients who are unwilling to sign the inform consent;
• Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) > 2 times upper normal limits; creatinine clearance rate < 60ml/min;
• Patients who used cyclophosphamide 6-months before screening; used biological agents 12-months before screening;
• Previous exposure of metformin within 30 days before screening; or previous history of intolerant to metformin;
• Patients who diagnosed of diabetes mellitus;
• Pregnancy or lactation.