Long-term effects of metformin use in gestational diabetes mellitus on offspring health

Abstract

Metformin is the first-line drug for the treatment of type 2 diabetes mellitus, but its role in gestational diabetes mellitus (GDM) management is not clear. Recent evidence suggests a certain beneficial effect of metformin in the treatment of GDM, but a high treatment failure rate leads to the initiation of additional medications, such as insulin. Moreover, since metformin crosses the placental barrier and reaches a significant level in the fetus, it is likely to influence the fetal metabolic milieu. The evidence indicates the long-term safety in children exposed to metformin in utero except for mild adverse anthropometric profiles. Diligent follow-up of metformin-exposed offspring is warranted from the clinician’s point of view.

Metformin With or Without Clomiphene Citrate Versus Laparoscopic Ovarian Drilling With or Without Clomiphene Citrate to Treat Patients With Clomiphene Citrate-Resistant Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

“…Most medications prescribed for pregnant and lactating women are “off-label” because most of the clinically approved medications do not have appropriate drug labeling information ( Ren et al, 2021 ). The limited evidence indicates the long-term safety of the fetus exposed to metformin excluding mild adverse anthropometric profiles (sex hormone binding globulin levels and long-term body mass index in offspring) ( Roy and Sahoo, 2021 ; Zhu et al, 2022 ). Although the FDA has not completely ruled out the risk of metformin in pregnancy, “these studies cannot establish the lacking metformin-associated risk because of methodological limitations, including the small sample size and inconsistent comparator groups” ( https://packageinserts.bms.com/pi/pi_glucophage.pdf ), many of the reviewed studies concluded that metformin is a safe choice at the beginning of pregnancy without persuasive evidence of increased risk for miscarriages or congenital malformations ( Quadir, 2021 ).…”