口服抗糖尿病药物与胰岛素治疗妊娠期糖尿病的疗效和安全性比较:一项更新的符合PRISMA标准的网状Meta分析。

Comparative efficacy and safety of oral antidiabetic drugs and insulin in treating gestational diabetes mellitus: An updated PRISMA-compliant network meta-analysis.

作者信息

Liang Hui-Ling, Ma Shu-Juan, Xiao Yan-Ni, Tan Hong-Zhuan

机构信息

Department of Epidemiology and Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.

出版信息

Medicine (Baltimore). 2017 Sep;96(38):e7939. doi: 10.1097/MD.0000000000007939.

Abstract

BACKGROUND

The safety and efficacy of different drugs in treatment of gestational diabetes mellitus (GDM) patients who could not maintain normal glucose level only through diet and exercise remains to be debated. We performed this network meta-analysis (NAM) to compare and rank different antidiabetic drugs in glucose level control and pregnancy outcomes in GDM patients.

METHODS

We searched PubMed, Cochrane Library, Web of Science, and Embase up to December 31, 2016. Randomized controlled trials (RCTs) related to different drugs in the treatment of GDM patients were enrolled. We extracted the relevant information and assessed the risk of bias with the Cochrane risk of bias tool. We did pair-wise meta-analyses using the fixed-effects model or random-effects model and then adopted random-effects NAM combining both direct and indirect evidence within a Bayesian framework, to calculate the odds ratio (OR) or standardized mean difference (SMD) and to draw a surface under the cumulative ranking curve of the neonatal and maternal outcomes of different treatments in GDM patients.

RESULTS

Thirty-two randomized controlled trials (RCTs) were included in this NAM, including 6 kinds of treatments (metformin, metformin plus insulin, insulin, glyburide, acarbose, and placebo). The results of the NAM showed that regarding the incidence of macrosomia and LGA, metformin had lower incidence than glyburide (OR, 0.5411 and 0.4177). In terms of the incidence of admission to the NICU, insulin had higher incidence compared with glyburide (OR, 1.844). As for the incidence of neonatal hypoglycemia, metformin had lower incidence than insulin and glyburide (OR, 0.6331 and 0.3898), and insulin was lower than glyburide (OR, 0.6236). For mean birth weight, metformin plus insulin was lower than insulin (SMD, -0.5806), glyburide (SMD, -0.7388), and placebo (SMD, -0.6649). Besides, metformin was observed to have lower birth weight than glyburide (SMD, 0.2591). As for weight gain, metformin and metformin plus insulin were lower than insulin (SMD, -0.9166, -1.53). Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight. Besides, insulin had the highest incidence of NICU admission, acarbose had the lowest risk of neonatal hypoglycemia.

CONCLUSION

Our study concluded that metformin is fastest in glucose control, with a more favorable pregnancy outcomes-would be a better option, but its rate of glucose control is the lowest.However, glyburide is the optimumtreatment regarding the rate of glucose control, but withmore adverse outcomes. This NAMbased on 32 RCTs will strongly help to guide further development of management for GDM patients, clinicians should carefully balance the risk-benefit profile of different treatments according to various situations.

摘要

背景

对于仅通过饮食和运动无法维持正常血糖水平的妊娠期糖尿病(GDM)患者,不同药物治疗的安全性和有效性仍存在争议。我们进行了这项网络荟萃分析(NAM),以比较和排序不同抗糖尿病药物在GDM患者血糖控制和妊娠结局方面的效果。

方法

我们检索了截至2016年12月31日的PubMed、Cochrane图书馆、科学网和Embase。纳入了与不同药物治疗GDM患者相关的随机对照试验(RCT)。我们提取了相关信息,并使用Cochrane偏倚风险工具评估偏倚风险。我们使用固定效应模型或随机效应模型进行成对荟萃分析,然后采用随机效应NAM,在贝叶斯框架内结合直接和间接证据,计算比值比(OR)或标准化均值差(SMD),并绘制GDM患者不同治疗方法新生儿和母亲结局累积排名曲线下的面积。

结果

该NAM纳入了32项随机对照试验(RCT),包括6种治疗方法(二甲双胍、二甲双胍加胰岛素、胰岛素、格列本脲、阿卡波糖和安慰剂)。NAM结果显示,就巨大儿和大于胎龄儿(LGA)的发生率而言,二甲双胍的发生率低于格列本脲(OR分别为0.5411和0.4177)。在新生儿重症监护病房(NICU)入院率方面,胰岛素的发生率高于格列本脲(OR为1.844)。至于新生儿低血糖的发生率,二甲双胍的发生率低于胰岛素和格列本脲(OR分别为0.6331和0.3898),且胰岛素低于格列本脲(OR为0.6236)。对于平均出生体重,二甲双胍加胰岛素低于胰岛素(SMD为-0.5806)、格列本脲(SMD为-0.7388)和安慰剂(SMD为-0.6649)。此外,观察到二甲双胍的出生体重低于格列本脲(SMD为0.2591)。在体重增加方面,二甲双胍和二甲双胍加胰岛素低于胰岛素(SMD分别为-0.9166、-1.53)。排名结果显示,就平均血糖控制而言,格列本脲可能是最佳治疗方法,而二甲双胍对GDM患者血糖控制最快;格列本脲的巨大儿、先兆子痫(PIH)、高胆红素血症、新生儿低血糖发生率最高,分娩时孕周最短,平均出生体重最低;二甲双胍(必要时加胰岛素)的巨大儿、PIH、LGA、呼吸窘迫综合征(RDS)、分娩时孕周小和低出生体重发生率最低。此外,胰岛素的NICU入院率最高,阿卡波糖的新生儿低血糖风险最低。

结论

我们的研究得出结论,二甲双胍血糖控制最快,妊娠结局更有利,是更好的选择,但其血糖控制率最低。然而,格列本脲在血糖控制率方面是最佳治疗方法,但不良结局更多。这项基于32项RCT的NAM将有力地帮助指导GDM患者管理的进一步发展,临床医生应根据各种情况仔细权衡不同治疗方法的风险效益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2e/5617694/a92175fea6c7/medi-96-e7939-g001.jpg

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