The evolving role of targeted metformin administration for the prevention and treatment of endometrial cancer: A systematic review and meta-analysis of randomized controlled trials

Abstract

Aim: The aim of the present study was to evaluate the role of metformin in endometrial cancer (EC), focusing on its potential preventive effect in breast cancer and obese patients and its safety and efficacy when added to progesterone monotherapy in EC patients who wish to preserve their fertility.

Methods: We reviewed the literature and then conducted a meta-analysis of the relevant parameters.

Results: A total of 6 studies was included in the meta-analysis. Regarding the pre-surgical treatment with metformin versus placebo, meta-analysis of mean difference in Ki-67 after treatment among two groups, revealed no difference (MD -7.10, 95% CI -23.31 to 9.11, p = 0.39). Meta-analysis of fertility sparing EC management with a combination of megestrol acetate (MA) and metformin (500 mg three times a day) in comparison with monotherapy with 160 mg daily MA revealed no difference in either complete response or partial response rates (166 patients OR 2.94, 95% CI 0.85 to 10.15, p = 0.09 and 166 patients OR 0.76, 95% CI 0.34 to 1.66, p = 0.49, respectively). As far as breast cancer survivors under tamoxifen are concerned, metformin was associated with significantly reduced median endometrial thickness after 52 weeks of evaluation compared to women in placebo group (2.3 mm vs 3.0 mm, p = 0.05).

Conclusions: Metformin neither was found to be an anti-proliferative agent against the development of endometrial cancer nor beneficial in addition to the progesterone monotherapy for EC fertility sparing candidates. However, a protective effect of metformin was demonstrated in breast cancer survivors under tamoxifen. Clinical outcomes of the ongoing trials are warranted to evaluate the therapeutic use of metformin in EC.

Keywords: Conservative treatment; Endometrial cancer; Metformin; Prevention.