Stopping diabetes, weight-loss drugs before pregnancy may raise health risks: Study

A new analysis has found that women who stop using popular GLP-1 drugs, which help manage type-II diabetes and obesity, before or early in pregnancy may face higher risks of several pregnancy-related complications. The study titled 'Gestational Weight Gain and Pregnancy Outcomes After GLP-1 Receptor Agonist Discontinuation' was published in JAMA Network. It looked at health records of women who had been prescribed GLP-1 receptor agonists such as semaglutide, tirzepatide and liraglutide.

These drugs are widely used for diabetes control and weight loss, but are not advised during pregnancy because of concerns seen in animal studies. Drug labels recommend stopping them at least two months before a planned pregnancy.

The new analysis included 1,792 matched pregnancies from the Mass General Brigham health system in the United States. Of these, 448 pregnancies had been exposed to a GLP-1 drug and later discontinued, while 1,344 pregnancies had no exposure. Most women who had used the drugs stopped before conception, and 17 per cent stopped after they became pregnant.

Researchers found that women who had used a GLP-1 drug and then stopped gained an average of 7.1 pounds more during pregnancy than those who had never used it. The exposed group gained 30.2 pounds on average compared to 23.1 pounds in the unexposed group.

The study also found higher rates of several complications among women who had stopped the medication. Excess gestational weight gain was seen in 65 per cent of the exposed group compared to 49 per cent of the unexposed group. Preterm delivery occurred in 17 per cent of exposed pregnancies versus 13 per cent in unexposed pregnancies. Gestational diabetes was reported in 20 per cent of the exposed group compared with 15 per cent of the unexposed group. Hypertensive disorders of pregnancy were seen in 46 per cent of the exposed group versus 36 per cent of the unexposed group.

The study team, led by Dr Jacqueline Maya of Massachusetts General Hospital, said these findings suggest that stopping GLP-1 drugs may lead to metabolic changes during pregnancy. She said that many people use these medicines before pregnancy and see significant benefits, but may face new risks when they stop using these as required.

According to the study, birth outcomes showed few differences between the two groups. Average birth weight percentile was slightly higher in the exposed group, but there were no differences in birth length, rates of babies being large or small for gestational age, or rates of caesarean delivery.

A supporting editorial noted that obesity and related health conditions were already linked to higher risks of miscarriage, preterm birth, gestational diabetes and preeclampsia. It said that while lowering body weight before pregnancy may reduce some risks, stopping GLP-1 drugs can lead to weight regain, and this period may overlap with early pregnancy.

The editorial also highlighted that semaglutide had a long half-life, which means the drug stays in the body for weeks. Because of this, guidelines advise stopping the drug two months before pregnancy. They said that more research is needed to understand how to manage patients who stop the medication and how to balance the benefits and risks for those planning a pregnancy.

The study had some limitations, including that researchers could not confirm how regularly patients took their medications. The analysis also matched women based on pre-pregnancy BMI rather than their BMI before starting GLP-1 treatment.

Researchers said further studies are needed to identify the best timing for stopping GLP-1 drugs and to understand long-term effects on mothers and infants.