Bidhendi Yarandi Razieh, Behboudi-Gandevani Samira, Amiri Mina, Ramezani Tehrani Fahimeh
1Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, P.O.Box: 19395-4763, Tehran, Iran.
2Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Diabetol Metab Syndr. 2019 Jul 23;11:58. doi: 10.1186/s13098-019-0453-7. eCollection 2019.
The results of studies that assessed the impact of metformin treatments on gestational diabetes mellitus (GDM) in patients with polycystic ovary syndrome (PCOS) are inconclusive. In addition, the impact of time and duration of metformin therapy for an optimum reduction of GDM has not been reported in these studies. This study aimed to summarize current knowledge regarding the effect of metformin-therapy before conception versus throughout pregnancy on the risk of GDM in women with PCOS. PubMed, Scopus, Google Scholar and ScienceDirect databases were searched to identify relevant studies. Both fixed and random effect models were used. Subgroup analyses were performed based on the on the study methodology. The association between the PCOS status and GDM was assessed using the univariate and multiple meta-regression analysis adjusted by the BMI and metformin therapy. Forty-eight of 1397 identified studies were included involving 5711 PCOS patients and 20,296 controls. Regardless of metformin therapy, the prevalence of GDM diagnosed in the second trimester among women with PCOS was significantly higher than healthy controls that was independent of obesity. Including all studies, the increased risk of GDM among women with PCOS, compared to healthy controls, disappeared after the adjustment of metformin-therapy (β = 0.08, 95% CI 0.04, 0.2; p = 0.624). By excluding observational studies as a source of bias, the prevalence of GDM among women with PCOS treated using metformin before conception till the end of pregnancy did not differ from treated just before conception (β = - 0.09, 95% CI - 0.2, 0.02; p = 0.092) or those without metformin therapy (β = - 0.05, 95% CI - 0.07, 0.04; p = 0.301). The results remained unchanged after the subgroup analysis based on the methodology of RCTs and non-RCTs studies. The main body of literature in the current meta-analysis was observational, which may be mixed with some sources of bias. Also, a lack of well-designed and high quality interventional studies means that the findings should be interpreted with cautious. In this respect, decisions regarding the continuation or discontinuation of metformin therapy in women with PCOS are somewhat arbitrary and can be made individually based on the patient's condition given the presence or absence of other GDM risk factors. Additional well-designed RCTs still need for precise recommendation.
评估二甲双胍治疗对多囊卵巢综合征（PCOS）患者妊娠期糖尿病（GDM）影响的研究结果尚无定论。此外，这些研究中尚未报道二甲双胍治疗的时间和持续时间对GDM最佳降低效果的影响。本研究旨在总结目前关于孕前与孕期全程使用二甲双胍治疗对PCOS女性发生GDM风险影响的相关知识。通过检索PubMed、Scopus、谷歌学术和ScienceDirect数据库来识别相关研究。使用固定效应模型和随机效应模型。根据研究方法进行亚组分析。采用单因素和多因素Meta回归分析评估PCOS状态与GDM之间的关联，并对BMI和二甲双胍治疗进行校正。在1397项已识别的研究中，纳入了48项研究，涉及5711例PCOS患者和20296例对照。无论是否接受二甲双胍治疗，PCOS女性在孕中期诊断出的GDM患病率均显著高于健康对照，且与肥胖无关。纳入所有研究后，与健康对照相比，PCOS女性发生GDM的风险增加在调整二甲双胍治疗后消失（β = 0.08，95%CI 0.04，0.2；p = 0.624）。通过排除作为偏倚来源的观察性研究，孕前至妊娠结束使用二甲双胍治疗的PCOS女性中GDM的患病率与仅在孕前治疗的女性（β = -0.09，95%CI -0.2，0.02；p = 0.092）或未接受二甲双胍治疗的女性（β = -0.05，95%CI -0.07，0.04；p = 0.301）相比无差异。根据随机对照试验（RCT）和非RCT研究方法进行亚组分析后，结果保持不变。当前Meta分析中的主要文献为观察性研究，可能混杂了一些偏倚来源。此外，缺乏设计良好且高质量的干预性研究意味着研究结果应谨慎解读。在这方面，鉴于存在或不存在其他GDM风险因素，关于PCOS女性继续或停止使用二甲双胍治疗的决策有些随意，可根据患者情况个体化做出。仍需要更多设计良好的RCT来给出精确建议。
