The association between metformin therapy and risk of gynecological cancer in patients: Two meta-analyses

Background: Recently, metformin, first-line drug for type 2 diabetes, has been reported to treat some gynecological tumors. However, these epidemiological studies have never been formally summarized. Considering a single study may lack the power to provide reliable conclusion, we performed two meta-analyses with different indicators to assess metformin's role in reducing the risk of gynecological cancers. Materials and methods: A systematic literature search was carried out in PubMed, Medline (Ovid), Embase database (last search was performed on August 15, 2018). The relative risk (RR) along with a random effects model were performed on Revman 5.3 and STATA 15.1 for risks analyzing. Results: A total of 1,710,080 patients in 7 studies were included in first meta-analysis. The results suggested metformin may reduce the risk of gynecological cancers (RR=0.49, 95%CI=0.29-0.82, and p=0.006). In the subgroup analyses: significantly decreased risks were found among Asians (RR=0.27, 95% CI=0.17-0.41, and p<0.00001), ovarian cancer (RR=0.18, 95%CI=0.12 -0.28, and p<0.00001), and cervical cancer (RR=0.60, 95%CI =0.43 -0.83, and p=0.002), but not in Caucasians (RR=0.81, 95%CI=0.50-1.32, and p=0.40) or in endometrial cancer (RR=0.71, 95%CI=0.29-1.74, and p=0.45). Meanwhile, another total of 8,335,332 cumulative follow-up years, person years, were conducted in 8 studies. The results indicated no statistical significance in general (RR=0.59, 95%CI=0.32-1.10, p=0.10), and no difference in Caucasians (RR=1.15, 95%CI=0.88 -1.48, and p=0.30), endometrial cancer (RR=0.89, 95%CI=0.27 -2.95, and p=0.84) or ovarian cancer (RR=0.37, 95%CI=0.09-1.49, and p=0.16) when performing subgroup analyses. However, in the subgroup analyses, results in Asians (RR=0.26, 95%CI=0.17-0.40, and p<0.00001) and cervical cancer (RR=0.56, 95%CI=0.40 -0.78, and p=0.0005) had an apparent significance. Conclusions: The results suggested the metformin can be used as a potential anticarcinogenic drug for gynecological cancers' prevention, especially for Asians and cervical cancer. The question remains, still, whether metformin is beneficial for ovarian cancer. Also, we don't know whether it is worth to give metformin to non-diabetes to prevent gynecological cancer. (C) 2019 Elsevier B.V. All rights reserved.