Could Metformin Become a Treatment for Gestational Diabetes?
By April Hopcroft
Metformin hasn’t generally been used to treat gestational diabetes because it crosses the placenta and might affect the fetus. But recent research suggests metformin could be comparable to insulin – plus, it’s much more convenient.
While the first course of action for managing gestational diabetes (GDM) involves diet and physical activity, diabetes medications like insulin are also used to manage the condition.
Traditionally, metformin has not been used as an initial treatment for GDM, as this medication can cross the placenta and could therefore cause neonatal hypoglycemia (low blood sugar at birth). Exposure to metformin during pregnancy can also affect the future health of babies.
"The concern with metformin is that it crosses to the placenta. Studies have shown children born to women who took metformin had higher rates of diabetes and obesity compared to those that didn't," said Dr. Diana Isaacs, director of education and training in diabetes technology at Cleveland Clinic.
Metformin is approved to treat type 2 diabetes but not GDM. Thus, using metformin in GDM is considered “off label,” meaning that a healthcare provider is prescribing a drug that hasn’t been FDA approved for this specific condition.
However, results from a recent study called SUGAR-DIP suggest that metformin is similarly effective to insulin for gestational diabetes, while also offering greater convenience and satisfaction for patients.
How did the study work?
The SUGAR-DIP trial included over 800 pregnant women who were unable to achieve healthy blood sugar levels with diet alone. The participants were randomly assigned to one of two groups: the first group received metformin (with a sulfonylurea or insulin, if needed) while the second group only received insulin. On average, participants were about 33 years old, and nearly 60% were white.
The researchers focused mainly on infant outcomes – specifically, newborns that were large for gestational age (LGA), or babies that weighed more than expected for the number of weeks of pregnancy. Giving birth to a LGA baby increases the risk of pregnancy complications, including injury during birth for both the baby and the mother, and also increases the chance of the mother needing a Cesarean section.
What were the key findings?
Nearly 24% of mothers treated with metformin gave birth to LGA babies, compared to 20% in the insulin treatment group. In other words, the study showed that metformin and insulin treatment were similar in terms of infant outcomes.
However, the researchers found several promising findings for maternal health:
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Participants receiving metformin had less maternal weight gain, compared to those taking insulin.
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While both groups reported high treatment satisfaction, participants receiving metformin were more likely to recommend their treatment to others and continue their treatment compared to those receiving insulin. This could be due to the fact that metformin is a pill that is simple to take, whereas insulin therapy involves multiple injections each day.
More side effects were reported among mothers treated with metformin compared to those treated with insulin, though serious side effects were similar in both groups.
Previous research has also shown benefits of metformin for diabetes in pregnancy
Perhaps the most well known study is the Metformin in women with type 2 diabetes in pregnancy trial (MiTy), which compared treatment with insulin alone and insulin with metformin among 500 pregnant women with type 2 diabetes.
Overall, the group receiving metformin and insulin had improved glycemic control and fewer LGA infants compared to those receiving insulin treatment alone. However, there was a greater proportion of small for gestational age (SGA) babies in the metformin group compared to the insulin only group.
A follow-up analysis of MiTy participants found no significant differences in BMI or estimated body fat among the 283 children studied at 24 months. According to gestational diabetes researchers Dr. Claire Meek and Dr. Laura Kusinski, these findings are reassuring, as they suggest that the benefits of metformin in pregnant women outweigh the risks.
A more recent study, conducted in Ireland, compared metformin versus placebo and found that early use of metformin did not lead to improvements in insulin initiation or reduce fasting glucose levels in the third trimester of pregnancy. However, participants who received metformin had less weight gain, with no evidence of an increase in preterm births. Additionally, the metformin group was 25% less likely to need insulin and, when insulin was required, these participants tended to start it later in pregnancy.
The bottom line
In the end, 20% of SUGAR-DIP participants in the metformin group needed insulin therapy (despite taking metformin as an initial treatment). Previous research has found that about half of pregnant women taking metformin end up requiring insulin, Isaacs said.
Despite the foundational role of insulin in managing GDM, there is room for better treatment options. Whereas insulin therapy involves multiple daily injections, plus extra education and adjustments, metformin is an oral drug that is straightforward and discreet to take. Metformin therefore has the potential to reduce stress and stigma for patients, which could lead to more consistent use of medication and better health outcomes for mom and baby.
"In many ways, I wish that metformin was the first line [option] because it would be so much easier than trying to sell people on starting insulin," Isaacs said. "And also much easier to start a pill versus teaching injection technique, timing of insulin, treatment of hypoglycemia, etc."
While more large-scale studies are needed to understand metformin’s safety and efficacy in GDM, these results highlight the importance of considering the patient’s perspective including satisfaction with treatment.
Note that GDM refers to diabetes that was not present prior to pregnancy and usually resolves after pregnancy. The term GDM does not apply to pregnant people who have previously been diagnosed with diabetes; treatment before, during, and after pregnancy is required in these cases.
Learn more about managing gestational diabetes:
