Diabetes Drug May Prevent Preterm Births

Metformin may help reduce rates of premature births and miscarriages.

Metformin is commonly used to treat type 2 diabetes, but an early-stage study revealed that it may also help prevent preterm births.

A study published in JCI: The Journal of Clinical Investigation analyzed mice bred to lack the gene p53 in the uterus, a condition known to cause premature birth, in order to determine why this occurs.

The findings revealed that when the p53 gene was removed, the decidual cells showed increased activity of the protein complex, mammalian target of rapamycin complex 1 (mTORC1). Furthermore, there was also a reduction in the activity of the signaling protein AMP-activated protein kinase (AMPK).

When these 2 changes occur, it can lead to premature cellular aging in the decidua and can end up fooling the mother’s body into going into labor, according to the study. The faster this process occurs, the higher risk of a miscarriage or premature birth.

After further research, the protein sestrin 2 was found to play a critical role in coordinating the relationship between AMPK and mTORC1 signaling. The levels of sestrin 2 were also found to decline in modified mice who were missing the p53 gene.

Once the laboratory mice were treated with metformin, the results of the study showed that the popular diabetes drug reversed the early aging cycle, and caused sestrin 2 levels and AMPK activity to increase, while mTORC1 signaling decreased. The mice treated with metformin ended up having full-term births.

Similar results, although less effective, were reported in mice treated with the antioxidant and anti-aging dietary supplement resveratrol.

Prior research has shown that rapamycin may have promise in the prevention of preterm birth in mice. However, the medication may be risky for use in pregnant women, according to the study. The authors noted that metformin seems to be a potentially safer alternative that works along the same molecular pathway.

“This proof-of-concept study illuminates a potential mechanism behind preterm birth,” said senior study author Sudhansu K. Dey, PhD. “It also demonstrates possible remedies that are already approved for human use.”

The findings are notable because it provides more detail on a little-known molecular pathway that can lead to premature birth, and also demonstrated 2 successful methods for restoring the function of the uterus lining to achieve healthy, full-term births.

Currently, other researchers are studying metformin and resveratrol as potential anti-aging drugs. However, the authors said they have yet to find any human clinical trials that are examining these medications for the use in preventing premature births.

The work to advance the findings into a treatment available for would-be mothers at risk of a preterm birth would require extensive work, the study noted. Furthermore, preparing and conducting human clinical trials could take several years.

However, experts trying to reduce high premature birth rates across the United States believe the new findings merit further investigation.

“I think the study has interesting implications,” said Louis Muglia, MD, PhD, director of the Center for Prevention of Preterm Birth at Cincinnati Children’s. “It forms the first step in a potential new intervention that would have to be carefully evaluated in human clinical trials. Metformin has been widely used, but only to a limited extent in pregnancy. Future studies will be needed.”