Metformin for pregnancy and beyond: the pros and cons

Newman, Christine; Dunne, Fidelma

doi:10.1111/dme.14700

Cited by 19 publications

(12 citation statements)

References 60 publications

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“…It is important to note that metformin is increasingly being used during pregnancy for the management of gestational diabetes mellitus and in those with polycystic ovary syndrome or T2DM 15 . As metformin crosses the placenta and circulates in the developing fetus, the long-term effects of fetal exposure to metformin have raised concerns about the potential risk to growth and development of the fetus, and later, on offspring health 16 .…”

Section: Introductionmentioning

confidence: 99%

Metformin: update on mechanisms of action and repurposing potential

2023

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Currently, metformin is the first-line medication to treat type 2 diabetes mellitus (T2DM) in most guidelines and is used daily by >200 million patients. Surprisingly, the mechanisms underlying its therapeutic action are complex and are still not fully understood. Early evidence highlighted the liver as the major organ involved in the effect of metformin on reducing blood levels of glucose. However, increasing evidence points towards other sites of action that might also have an important role, including the gastrointestinal tract, the gut microbial communities and the tissue-resident immune cells. At the molecular level, it seems that the mechanisms of action vary depending on the dose of metformin used and duration of treatment. Initial studies have shown that metformin targets hepatic mitochondria; however, the identification of a novel target at low concentrations of metformin at the lysosome surface might reveal a new mechanism of action. Based on the efficacy and safety records in T2DM, attention has been given to the repurposing of metformin as part of adjunct therapy for the treatment of cancer, age-related diseases, inflammatory diseases and COVID-19. In this Review, we highlight the latest advances in our understanding of the mechanisms of action of metformin and discuss potential emerging novel therapeutic uses.

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Section: Introductionmentioning

confidence: 99%

Metformin: update on mechanisms of action and repurposing potential

2023

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“…An interesting review recently published proposed a clinical targeted approach in the use of metformin in pregnant women ( 74 ).…”

Section: Discussionmentioning

confidence: 99%

Lights and shadows on the use of metformin in pregnancy: from the preconception phase to breastfeeding and beyond

et al. 2023

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During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing in vitro fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk.

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“…Adverse effects included abdominal pain, diarrhea, or headache were reported in women receiving metformin compared with women receiving placebo cumulatively (RR 1.63, 95% CI 1.27–2.08; 1 study, 400 women) [ 24 ]. In a recent review by Dunne about the metformin in pregnancy, all the different results in maternal outcomes observed in these RCTs were attributable to patient characteristics: all Caucasian women in the EMPOWaR study whereas the MOP trial had more ethnic diversity; in the GRoW study the BMI was 32.5 kg/m 2 , compared to 38 kg/m 2 in EMPOWaR and 38.6 kg/m 2 in MOP and in the medication dosage (the maximum dose of metformin was 2500 mg in the EMPOWaR, in the MOP trial 3000 mg, and in the GRoW study 2000 mg) [ 26 ]. We did not identify studies of metformin in combination with another treatment in obese women in pregnancy.…”

Section: Metformin In Pregnancy Complicated By Obesity and Overweight...mentioning

confidence: 99%

Position paper of the Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), and the Italian Study Group of Diabetes in pregnancy: Metformin use in pregnancy

et al. 2023

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Objective This document purpose is to create an evidence-based position statement on the role of metformin therapy in pregnancy complicated by obesity, gestational diabetes (GDM), type 2 diabetes mellitus (T2DM), polycystic ovary syndrome (PCOS) and in women undergoing assisted reproductive technology (ART). Methods A comprehensive review of international diabetes guidelines and a search of medical literature was performed to identify studies presenting data on the use of metformin in pregnancy. The document was approved by the councils of the two scientific societies. Results In condition affecting the fertility, as PCOS, metformin use in pre-conception or early in pregnancy may be beneficial for clinical pregnancy, even in ART treatment, and in obese-PCOS women may reduce preterm delivery. In obese women, even in the presence of GDM or T2DM, metformin use in pregnancy is associated with a lower gestational weight gain. In pregnancy complicated by diabetes (GDM or T2DM), metformin improves maternal glycemic control and may reduce insulin dose. Neonatal and infant outcomes related to metformin exposure in utero are lacking. Metformin use in women with GDM or T2DM is associated with lower birth weight. However, an increased tendency to overweight–obesity has been observed in children, later in life. Conclusions Metformin may represent a therapeutic option in selected women with obesity, PCOS, GDM, T2DM, and in women undergoing ART. However, more research is required specifically on the long-term effects of in utero exposition to metformin.

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Metformin for pregnancy and beyond: the pros and cons

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 19 publications

References 60 publications

Metformin: update on mechanisms of action and repurposing potential

Metformin: update on mechanisms of action and repurposing potential

Lights and shadows on the use of metformin in pregnancy: from the preconception phase to breastfeeding and beyond

Position paper of the Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), and the Italian Study Group of Diabetes in pregnancy: Metformin use in pregnancy

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