Although metformin crosses the placenta and produces similar plasma concentrations in mother and fetus, it is safe for use during pregnancy (FDA Category B).
In addition, hyperglycemia in pregnancy is a proven risk factor for congenital anomalies, so it is reasonable to use metformin for the treatment of gestational diabetes.
Read the article on estet-portal.com about studies on the efficacy and safety of metformin in time of pregnancy.
- Studies on Metformin versus Insulin
- Long-term effects of metformin on child development after treatment
- Metformin and neoplasms of the female genital organsin
Metformin versus insulin studies
In the JA Rowan study, women with gestational diabetes were randomized to either metformin or insulin.
Metformin treatment was well tolerated, gastrointestinal adverse reactions were the reason for discontinuation of the drug in only 1.9% of patients.
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Importantly, the incidence of severe hypoglycaemia (<1.6 mmol/l) was significantly lower in the metformin group.
Metformin treatment was well received by patients, with 76.6% of women willing to take metformin during their next pregnancy.
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Metformin was also associated with less weight gain during pregnancy compared with a group of women who corrected gestational diabetes used insulin.
A meta-analysis of studies in women previously diagnosed with polycystic ovary syndrome showed that treatment with metformin was associated with a 14% reduction in the risk of congenital anomalies.
A recent meta-analysis confirmed the safety of metformin as 1st line therapy for gestational diabetes, as well as the preference for metformin over the other single oral antidiabetic drug previously approved for use in pregnancy, − glibenclamide.
Most women with type 2 diabetes diagnosed before pregnancy require continued metformin treatment during pregnancy to maintain glycemic control (especially in the III trimester, when there is a physiological increase in insulin resistance).
According to Hughes and Rowan, treatment with metformin in women with pregestational type 2 diabetes was not associated with worsening of any pregnancy outcomes and.
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Long-term effects of metformin on child development after treatment
A large study of MiG TOFU assessed the long-term prognosis of children exposed to metformin in utero compared with the insulin group.
According to this study, at 2 years of age, children treated with metformin in utero had more thick skinfold in the area of the shoulder and scapula compared with children whose mothers received insulin therapy during pregnancy; while the total fat content was the same in both groups.
This indicates a more favorable type of distribution of adipose tissue (by subcutaneous rather than visceral type) in metformin treatment.
Another prospective study in children of mothers with PCOS who took metformin from early pregnancy showed no adverse effects on anthropometric data, motor activity and behavioral responses in these children at 18 monthsc.
Metformin and female genital neoplasms
By reducing the carcinogenic effects of obesity and insulin resistance, metformin may be used for long-term chemoprophylaxis in women at increased risk of developing endometrial cancerandbreast.
This group primarily includes women with:
- polycystic ovary syndrome;
- morbid obesity;
- impaired glucose tolerance;
- endometrial hyperplasia.
In addition to influencing body weight and insulin resistance, metformin can regulate the cell cycle by interacting with classical oncogenes and tumor suppressors.
For example, metformin has been shown to induce AMPK-dependent downregulation of c-MYC in breast cancer cell lines.
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This effect is mediated by increased miRNA expression, which in turn is mediated by increased regulation of the RNase enzyme III Dicer in response to metformin treatment.
Modulation of Dicer by metformin is of particular importance given that low levels of this enzyme are associated with poor prognosis in ovarian, breast, and lung cancers.
Metformin has also been found to impair folate and methionine metabolism in breast cancer cells with a simultaneous decrease in glutathione and tryptophan metabolites.
In studies in women with endometrial cancer, overall survival was significantly better in patients with type 2 diabetes treated with metformin compared with women with or without diabetes, who were not taking metformin.
This correlation was statistically significant after adjusting for age, clinical stage of cancer, histologic grade, and use of adjuvant therapy.
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