Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly prescribed to manage type 2 diabetes and obesity. However, these medications are not recommended during pregnancy. A recent study in JAMA Network Open examined whether discontinuing GLP-1 RAs before conception affects pregnancy weight gain and related outcomes.
Weight Gain Concerns in Pregnancy
The prevalence of obesity among pregnant women in the U.S. has risen sharply, increasing the risk of developing type 2 diabetes during pregnancy—from 1.8 per 1,000 births in 2000 to 7.3 per 1,000 in 2019. Obesity and diabetes during pregnancy are linked to higher complication rates and long-term health risks for offspring.
While GLP-1 RAs are effective in controlling weight and blood sugar, they are not advised during pregnancy due to potential fetal effects seen in animal studies. Discontinuing these medications can lead to weight gain and elevated blood glucose levels. Excessive gestational weight gain increases the risk of high birth weight, preterm delivery, gestational diabetes, hypertensive disorders, and Cesarean delivery.
Study Design and Methods
Researchers conducted a retrospective analysis of 1,792 women with singleton pregnancies, comparing those previously exposed to GLP-1 RAs with those who were not. The study tracked gestational weight gain, birth weight and length, preterm birth, Cesarean delivery, gestational diabetes, and hypertensive disorders.
Findings: Higher Weight Gain and Pregnancy Risks
Among 448 women with prior GLP-1 RA use, the mean maternal age was 34 years, and the mean BMI was 36. Obesity affected 84% of these women, and 23% had diabetes before pregnancy. About two-thirds had discontinued GLP-1 RAs, mainly semaglutide, within six months of conception.
Women with previous GLP-1 RA exposure gained an average of 3.3 kg more than unexposed women. Approximately 65% were at risk of excessive weight gain, compared to 49% of controls. The risk of excessive weight gain was 32% higher among previously exposed women.
Babies born to exposed mothers had slightly higher birth weights, but rates of Cesarean delivery and large-for-gestational-age infants were not significantly different. However, the risk of gestational diabetes and hypertensive disorders was about 30% higher among the exposed group. These conditions also increased the likelihood of preterm birth, which was 34% higher among previously exposed women. The type of GLP-1 RA and timing of discontinuation did not significantly alter outcomes.
Implications and Future Research
The study suggests that pre-conception use of GLP-1 RAs, followed by discontinuation, may lead to greater gestational weight gain and higher risks of pregnancy complications. Since this was an observational study using electronic health records, results show associations rather than causation and may be influenced by residual confounding.
Further research is needed to determine how GLP-1 RA treatment before pregnancy—and its cessation—affects maternal weight, metabolic health, and long-term outcomes in children. These findings may inform future guidance on the use of GLP-1 RAs in women of childbearing age who may need to discontinue the drugs if they become pregnant.
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