Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Amsterdam Reproduction and Development, Amsterdam, The Netherlands.
Diabet Med. 2024 Feb;41(2):e15243. doi: 10.1111/dme.15243. Epub 2023 Oct 26.
The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes.
A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta-analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup.
We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow-up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta-analysis. No significant effects in the overall meta-analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between-studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details.
This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non-human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high-quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.
母亲在怀孕期间使用二甲双胍对胎儿、婴儿、儿童和青少年的生长、发育和健康的影响尚不清楚。我们的目的是系统地综述动物实验中关于宫内二甲双胍暴露对子代人体测量、心血管和代谢结果的影响的现有证据。
在 PUBMED 和 EMBASE 中进行了系统检索（搜索于 2023 年 4 月 12 日进行）。我们提取了原始的、对照动物研究，这些研究调查了母亲在怀孕期间使用二甲双胍对后代人体测量、心血管和代谢测量的影响。随后，对所有包含 3 项或更多研究数据的结果进行了风险偏倚评估和荟萃分析，使用标准化均数差和随机效应模型。如果每组有 10 个或更多的比较，则计划进行亚组分析，分析的内容为物种、品系、性别和模型类型。
我们纳入了 37 篇文章（n=3133 只后代来自 n=716 窝，包含 n=51 个比较），主要是（95%）啮齿动物模型和 5%猪模型。对后代的随访范围从出生到 2 岁。纳入的 34 篇文章可以进行荟萃分析。在总体荟萃分析中，二甲双胍对任何人体测量、心血管和代谢的后代结局指标都没有显著影响。由于缺乏对重要方法细节的报告，大多数研究的研究间异质性很高，且风险偏倚不明确。
本系统综述未能确定母亲在怀孕期间使用二甲双胍治疗对非人类后代的人体测量、心血管和代谢结果的影响。研究间异质性很高，而且由于对重要方法细节的报告有限，大多数研究的风险偏倚不明确。这突出表明需要在人类和模型系统中开展更多高质量的研究，以得出明确的结论。未来的研究应重点关注二甲双胍在年龄较大的后代群体中的作用，以及迄今为止尚未研究的结果。
