Effect of metformin on proliferative markers in women with endometrial carcinoma: Systematic review and meta-analysis

OBJECTIVE: Endometrial carcinoma (EC) is the most common gynecologic malignancy in the USA and Western Europe. Surgery is the mainstay of both staging and treatment of EC. Fertility sparing medical therapies are often offered to young women who desire fertility. Metformin has been suggested to be an anti-cancer agent as evidenced by previous studies. It decreases Antigen Ki-67 (Ki-67) proliferation and expression which is associated with proliferative activity of malignant tumors. In this systematic review and meta-analysis, we assessed the efficacy of metformin on patients with EC. MATERIALS AND METHODS: We searched PubMed, Cochrane CENTRAL, Web of Science, and SCOPUS for relevant clinical trials and excluded observational studies. The quality appraisal was evaluated according to GRADE, and we assessed the risk of bias using Cochrane’s risk of bias tool. We conducted the analysis of continuous data using mean difference (MD). We included the following outcomes: Ki-67 index, glucose, insulin, P-S6, body mass index (BMI), C-peptide, Insulin-like growth factor (IGF-1), leptin, and hemoglobin. RESULTS: Nine studies were eligible for our meta-analysis. We found that compared to the control group, metformin is highly effective in reducing Ki-67 proliferation and expression [MD=-10.14 (-19.10, -1.17)], (p=0.03), P-S6 [MD=-1.82 (-3.17, -0.46)], (p=0.009), plasma glucose level [MD=-1.76 (-4.88, 1.37), p=0.27], and BMI [MD=-1.07 (-1.49, -0.65)], (p<0.001). CONCLUSION: We conclude that metformin administration is effective in patients with EC. It decreases Ki-67 proliferation and expression, serum glucose, and p-S6 significantly.