Evaluation of Preeclampsia Results after Use of Metformin in Gestation: Systematic Review and Meta-analysis

Abstract

Objective Does the use of metformin have an influence on the outcomes of preeclampsia (PE)? Sources of Data The descriptors pregnancy, metformin, treatment, and preeclampsia associated with the Boolean operators AND and OR were found in the MEDLINE, LILACS, Embase and Cochrane databases. A flowchart with exclusion criteria and inclusion strategy using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, and eligibility criteria was used. Data were extracted regarding the type of study, the applied dosage, treatment time, segment, bias risks, and the Patient, Intervention, Comparison and Outcome (PICO) strategy to identify the quality of the study. Selection of Studies Total number of journals in the initial search (n ¼ 824); exclusions from repeated articles on different search engines (n ¼ 253); exclusions after reading the titles, when the title had no correlations with the proposed theme (n ¼ 164); exclusions due to incompatibility with the criteria established in the methodological analysis (n ¼ 185), exclusion of articles with lower correlation with the objective of the present study (n ¼ 187); and final bibliographic selection (n ¼ 35). Data Collection At first, a systematic review of the literature was performed. Subsequently, from the main selection, randomized and non-randomized trials with metformin that presented their results in absolute and relative numbers of PE outcomes were selected. The variables were treated statistically in the meta-analysis with the Review Manager software (RevMan), version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration. Denmark in the Hovedistaden region. Synthesis of Data The study showed that metmorfin presented greater preventive effects for pregnancy-induced hypertension and was less effective for PE.

Impact of metformin treatment during pregnancy on maternal outcomes: a systematic review/meta-analysis

“…Previous meta-analyses have explored the impact of metformin on pre-eclampsia risk, with mixed results [18,19,68]. At least one previous meta-analysis that included both GDM and non-GDM pregnancies and analysed both randomized and observational data [68] found no signi cant effect of metformin on pre-eclampsia risk, which is in keeping with our observation that pre-eclampsia risk is not reduced in euglycemic pregnancies.…”

“…Mechanistically, metformin may prevent pre-eclampsia via reduction of antiangiogenic factors, improvements of endothelial function via actions on the mitochondria and/or via actions through the mammalian target of rapamycin (mTOR) pathway by modi cation of cellular homeostasis and energy deposition [67]. Previous meta-analyses have explored the impact of metformin on pre-eclampsia risk, with mixed results [18,19,68]. At least one previous meta-analysis that included both GDM and non-GDM pregnancies and analysed both randomized and observational data [68] found no signi cant effect of metformin on pre-eclampsia risk, which is in keeping with our observation that pre-eclampsia risk is not reduced in euglycemic pregnancies.…”

Can Endothelial Glycocalyx Be A Major Morphological Substrate in Pre-Eclampsia?

“…Improves the eGC barrier properties [84] According to several studies, metformin may prevent or treat PE [85,86] N-acetylcystein Preserves eGC [87] Beneficial effect of the N-acetylcystein administration was noted in some clinical and experimental studies with PE [88][89][90] In mice with knockout of the Sdc-1 -/gene, in contrast to wild-type mice, FFP did not show any protective effect. It is believed that the effects of FFP are caused by certain components: albumin and adiponectin.…”

“…A systematic review and meta-analysis by Kalafat E et al (2018) provides evidence that there is a high probability that metformin use is associated with a reduced incidence of hypertensive disorders of pregnancy (HDP) especially in women with gestational diabetes and obesity, when compared with other treatments or placebo [85]. Another systematic review by Nascimento IBD et al (2018) showed that metformfin provided greater preventive effects for pregnancy-induced hypertension, i.e., for milder hypertensive syndromes, and was less effective in PE [86]. Unfortunately, the value of mentioned reviews is limited by the small number of studies included in the analysis, the low quality of evidence, and the clinical heterogeneity precluding generalization of these results to broader populations.…”

Anti–Glycation Aging Prevention Strategies

“…Міжнародна федерація діабету у своєму керівництві по цукровому діабету в 1999 році назвала метморфін першим у списку рекомендованих до використання пероральних цукрознижуючих препаратів. Встановлена його профілактична дія при гіпертонії, яка розвинулась на фоні вагітністі [34].…”