Metformin and Hypertensive Disorders of Pregnancy: A Phenotype-Based Focused Narrative Review

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Abstract
Background: Hypertensive disorders of pregnancy (HDP), particularly gestational hypertension and preeclampsia, are major causes of maternal and perinatal morbidity. Metabolic disorders such as gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), obesity, and polycystic ovary syndrome (PCOS) share mechanisms with HDP, including insulin resistance, inflammation, oxidative stress, endothelial dysfunction, and placental maladaptation. Metformin may influence these pathways, but its clinical effect on hypertensive outcomes remains uncertain. Methods: A focused narrative review was conducted using structured, targeted searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for literature published primarily from January 2015 through March 2026, supplemented by landmark studies, clinical guidelines, randomized trials, large observational cohorts, systematic reviews, meta-analyses, and mechanistic and placental studies. Evidence was selected for its relevance to the predefined phenotype-based framework and synthesized qualitatively across mechanistic, clinical, and translational domains. Results: Metformin improves insulin sensitivity and may reduce gestational weight gain, metabolic stress, inflammatory signaling, and oxidative stress. Some randomized trials and meta-analyses in GDM, obesity, and PCOS suggest lower rates of pregnancy-induced hypertension or preeclampsia, whereas recent randomized and population-based studies report neutral effects. Findings are limited by heterogeneous populations, late treatment initiation, variable comparators, supplemental insulin use, inconsistent HDP definitions, and insufficient statistical power. Conclusions: Metformin may act as a metabolic and vascular modifier in selected pregnancies, but current evidence does not support its routine use specifically for HDP prevention. Its public health value lies primarily in accessible metabolic treatment and integration into comprehensive antenatal and postpartum risk reduction pathways, rather than replacement of aspirin, blood pressure surveillance, or maternal–fetal monitoring.

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