THE ROLE OF METFORMIN- “aspirin of the 21st century” IN PREECLAMPSIA PROPHYLAXIS
The School of Medicine – VNU-HCM’s authors have reviewed recent worldwide studies on the role of Metformin in general, studies and clinical trials on the use of Metformin in treating and preventing preeclampsia in particular. The review aims to provide readers with an overview of the pathogenesis of preeclampsia, the mechanism of Metformin’s action, and the current evidence on the safety and efficacy of Metformin in the prevention and treatment of preeclampsia.
Preeclampsia (PE) is a principal cause of maternal and newborn mortality that poses financial and physical burdens to tens of thousands of families each year. Unfortunately, there is no effective management to arrest the progression of this disease unless delivery. Therefore, standardized management or preventive treatments are needed urgently. PE is closely associated with placental hypoxia, which increases the secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) as well as soluble endoglin (sEng) into the maternal circulation.
Although the recommended approach to screening for pre-eclampsia is blood pressure monitoring, the ASPRE trial has shown that it is possible to predict the development of early-onset preeclampsia with good precision using a combination of maternal factors and biomarkers in the first trimester of pregnancy. Early prediction is quite important as aspirin, the only proven preventative method for PE, has a dose- and time-dependent effect. Early detection and additional interventions could boost the beneficial effects of aspirin. However, only 12% of all preeclampsia cases are early-onset and prediction models show poorer precision for late-onset disease. Furthermore, aspirin failed to show a clinically meaningful effect on the development of late-onset PE, in which the majority of the disease burden lies. Therefore, a preventative method targeting both early- and late-onset PE is highly desirable.
Metformin is commonly used to treat type 2 diabetes. It improves insulin sensitivity (enhances peripheral glucose uptake and utilization), reduces the intestinal absorption of glucose, and reduces hepatic glucose production. Surprisingly, its role has been expanding to—but not limited to—the treatment of prediabetes, gestational diabetes, polycystic ovarian disease, congestive heart failure, chronic kidney disease, prolongation of lifespan, and reduction of breast and prostate cancer metastasis. Moreover, numerous experiments have suggested that metformin plays an important role in the treatment or prevention of PE. Metformin was proven that it could reduce soluble fms-like tyrosine kinase-1 levels, which correlate significantly with gestational age at onset of pre-eclampsia and severity. It has also been suggested that Metformin may prevent preeclampsia by improving cardiovascular function and limiting gestational weight gain. That the reasons why Metformin was called the “aspirin of the 21st century”.
MSc. MD. Pham Cong Toan, Obstetrics and Gynecology Department, the School of Medicine – Vietnam National University Ho Chi Minh City