Comparison of exenatide alone or combined with metformin versus metformin in the treatment of polycystic ovaries: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of childbearing age. Randomized controlled trials (RCTs) have reported that exenatide and metformin are effective in the treatment of PCOS. In this meta-analysis, we aimed to compare the effectiveness and safety of exenatide alone or in combination with metformin versus metformin in patients suffering from PCOS. METHODS: RCTs of exenatide therapy were identified through a search of electronic databases in November 2022 and updated in October 2023. Eligible studies were identified independently by the reviewers. Outcomes were analysed with Revman 5.4. RESULTS: Nine RCTs among 214 studies on 1059 women with PCOS were included in the analysis, and among the nine RCTs, eight studies compared exenatide with metformin. Our meta-analysis demonstrated that exenatide was more effective than metformin in terms of pregnancy rate (RR 1.85 [95% CI 1.19,2.86] P = 0.006), sex hormone-binding globulin (SHBG) (MD 5 [95% CI 3.82,6.18] P < 0.001), and follicle-stimulating hormone (FSH) (MD 0.82 [95% 0.41,1.24] P < 0.001). The reductions in total testosterone (TT) (SMD -0.43 [95% CI -0.84, -0.03] P = 0.04) was more significant after treatment with exenatide than after treatment with metformin. In terms of safety, exenatide had a lower diarrhea rate (RR 0.11 [95% CI 0.01, 0.84]) than metformin. In the other three studies, exenatide plus metformin was compared with metformin. Exenatide combined with metformin was more effective in improving SHBG (MD 10.38[95%CI 6.7,14.06] P < 0.001), Matsuda index (MD 0.21[95%CI 0.05,0.37]) and reducing free androgen index (FAI) (MD -3.34 [-4.84, -1.83] P < 0.001), Weight (MD -2.32 [95%CI -3.89, -0.66]) and WC (MD-5.61[95%CI -8.4, -2.82] P < 0.001). The incidence of side effects between exenatide plus metformin and metformin was not statistically significant. CONCLUSIONS: Exenatide alone or in combination with metformin is more effective than metformin for women with PCOS. Considering the evidence on effectiveness and safety, exenatide alone or in combination with metformin may be a better treatment approach than metformin for women with PCOS. TRIAL REGISTRATION: INPLASY https://inplasy.com/inplasy-protocols/ ID: 10.37766/inplasy2022.11.0055.