Is it safe to initiate metformin (biguanide oral hypoglycemic agent) in a postpartum patient?

From the Guidelines

Initiating metformin in a postpartum patient is safe and recommended, especially for those with a history of gestational diabetes mellitus (GDM), as it can reduce the progression to diabetes by 40% over 10 years, as shown in a study published in Diabetes Care in 2018 1. When considering metformin for a postpartum patient, several factors come into play, including the patient's medical history, current health status, and breastfeeding plans.

• The patient's history of GDM is a significant consideration, as metformin has been shown to reduce the risk of progressing to type 2 diabetes in these patients 1.
• For breastfeeding patients, metformin is considered compatible, as minimal amounts pass into breast milk, with no reported adverse effects in nursing infants.
• Common side effects of metformin include gastrointestinal disturbances like nausea, diarrhea, and abdominal discomfort, which can be minimized by starting with a low dose and taking it with food.
• Postpartum patients on metformin should be monitored for vitamin B12 deficiency with long-term use, and should be aware that metformin may increase fertility by improving ovulation, potentially leading to unplanned pregnancy.
• The typical starting dose of metformin is 500 mg once daily with a meal, gradually increasing to 500 mg twice daily after one week if tolerated, with a maximum dose of 2000-2500 mg daily divided into two or three doses.
• Metformin works by decreasing hepatic glucose production, reducing intestinal glucose absorption, and improving insulin sensitivity in peripheral tissues, making it effective for managing glucose levels while supporting postpartum metabolic health.
• According to the study published in Diabetes Care in 2018 1, lifestyle intervention and metformin can reduce the progression to diabetes by 35% and 40%, respectively, over 10 years compared to placebo, making it a valuable treatment option for postpartum patients with a history of GDM.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Safety of Metformin in Postpartum Patients

• Metformin is considered safe in the postpartum period, and it may reduce diabetes risk if started soon after delivery in individuals with gestational diabetes mellitus (GDM) 2.
• Studies have shown that metformin is not teratogenic and is safe to use throughout pregnancy, with no worsening of obstetric or perinatal outcomes 3.
• However, the long-term risks to the offspring remain inadequately researched, with no evidence of harm up to 2 years, and no suggestions of later complications in countries using metformin for many years 3.

Metformin Pharmacokinetics in Postpartum Period

• Serum metformin concentrations increase by 32% in the postpartum period compared to pregnancy, with this change occurring already during the first 2 weeks postpartum 4.
• Clinicians should be aware of the significant decrease in metformin concentration mediated by pregnancy and the rapid increase after delivery, as it may impact both the therapeutic efficacy and the risk of adverse drug reactions 4.

Benefits and Risks of Metformin in Pregnancy and Postpartum

• Metformin has been shown to reduce gestational weight gain, fetal size, and the risk of cesarean delivery, as well as lower rates of hypertension 5.
• However, metformin has been associated with increases in the risk of giving birth to small-for-gestational-age neonates and higher body mass index (BMI) z-scores among exposed offspring in some studies 5, 6.
• Despite these benefits and risks, metformin appears well tolerated in pregnancy and is more acceptable to women than insulin therapy, making it a reasonable intervention in a population affected by rising rates of obesity and diabetes in pregnancy 6.