Objective: To assess the efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC).

Design: A randomised, single-centre, open-label, controlled trial conducted between October 2013 and December 2017.

Setting: Shanghai OBGYN Hospital of Fudan University, China.

Population: A total of 150 patients (18-45 years old) with primary AEH or well-differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76).

Methods: Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day).

Main outcomes and measures: The primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w-CR rate); the secondary efficacy parameters were 30w-CR rate and adverse events.

Results: The 16w-CR rate was higher in the metformin plus MA group than in the MA-only group (34.3 versus 20.7%, odds ratio [OR] 2.0, 95% confidence interval [CI] 0.89-4.51, P = 0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06-6.21, P = 0.04). This effect of metformin was also significant in non-obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22-8.84, P = 0.02) and insulin-sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03-8.97, P = 0.04) subgroups of AEH women. No significant result was found in secondary endpoints.

Conclusion: As a fertility-sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients.

Tweetable abstract: For AEH patients, metformin plus MA might be a better fertility-sparing treatment to achieve a higher early CR rate compared with MA alone.