Weight Gain From Discontinuing GLP-1s a Concern in Pregnancy

ORLANDO, Florida — With glucagon peptide-1 receptor agonist (GLP-1 RA) drugs known to have a rapid rebound of weight gain upon discontinuation, women who stop using the drugs prior to pregnancy, as is recommended, show significantly greater pregnancy weight gain than those not exposed to the drugs, at a time when excessive weight gain presents added risks, new research showed.

“Many individuals exceed the body mass index (BMI)-based recommended gestational weight guidelines in pregnancy [upon discontinuation],” senior author Camille E. Powe, MD, an associate professor of Obstetrics, Gynecology and Reproductive Biology at Massachusetts General Hospital in Boston, told Medscape Medical News.

“Clinicians should counsel their patients that they may gain more weight during pregnancy if they use these medications before pregnancy,” she said.

The research was presented at the annual meeting of the American Diabetes Association (ADA) 84th Scientific Sessions.

The findings are from a retrospective cohort study that Powe and her colleagues conducted, which identified 188 singleton pregnancies between 2016 and 2022 among women with preexisting type 2 diabetes.

Women with and without prior GLP-1 RA use were matched 1:3 (one exposed pregnancy to three unexposed pregnancies) with propensity score matching on the basis of factors including prepregnancy BMI, maternal age, gestational age at delivery, race and ethnicity, and health insurance status.

In total, 47 had prepregnancy exposure to GLP-1 receptor agonists, and 141 had no exposure.

The women had a mean maternal age of 34.5 years and a mean prepregnancy BMI of 35.5.

The results showed that those with GLP-1 RA preexposure had a mean gestational weight gain of 24.9 lb vs a gain of 19.1 lb in the unexposed group (P = .03), with 61.7% in the GLP-1 RA-exposed group exceeding the recommended gestational weight gain vs 41.1% in the unexposed group (P = .02).

Excessive Weight Gain Concerns in Pregnancy

Specific concerns of excessive weight gain in pregnancy include that extra weight gain in pregnancy is linked to an increased risk for outcomes including gestational diabetes, macrosomia [giving birth to a baby > 4 kg], cesarean delivery, and hypertensive disorders of pregnancy, Powe explained.

“Each of these outcomes carries morbidity for the pregnant individual and their baby,” she said.

The recommendation to take an action that is almost guaranteed to cause rapid weight gain just before conception is therefore a significant risk for its own, Maisa N. Feghali, MD, an assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of Pittsburgh, Pittsburgh, added in speaking on the issue at the meeting.

“While this strategy may avoid direct drug exposure, it essentially sets up our patients to be in the most accelerated phase of weight gain just as they are embarking on their early pregnancy,” she said.

Furthermore, “we have to keep in mind that these are not patients that are going to go down to a baseline risk of the general population,” Feghali noted.

If untreated, “the baseline risk of hyperglycemia and type 2 diabetes or diabetes in general and pregnancy outcomes such as congenital malformations is quite significant,” she said.

Pregnancy Risks for GLP-1 RAs Unknown

Meanwhile, the risks for GLP-1 RAs in pregnancy have not been determined, and while some studies involving mice have suggested effects such as reduced fetal weight or growth rates, Feghali noted that those studies have had confounders such as mice receiving doses up to 10-fold higher than used in humans; their weight loss was, in some studies, more than 50%, which is not typically seen in humans, and most animal models did not have diabetes.

Until the true risks are understood, the recommendations not to use GLP-1s in pregnancy are clearly necessary, but yet another concern is exposure to the drugs in pregnancy, not because women intentionally ignored the recommendations but because they didn’t know they were pregnant.

Not only are unplanned pregnancies already exceptionally high, estimated at more than 50% in the United States, but that proportion could further rise if the suspicions are true about GLP-RAs having the additional effect of increasing fertility, a phenomenon dubbed “Ozempic babies.”

For those women, weeks may go by during the earliest stage of pregnancy in which there is maternal and fetal exposure to the drugs.

“Prenatal care often doesn’t start till about 8-10 weeks, so by the time patients have initiated their prenatal care, they’ve already gone through organogenesis, and any effect that has happened is already behind us, translating to unintended fetal exposures,” Fenghali said.

Asked by an audience member how she advises patients in terms of discontinuing the drugs while trying to prevent the excessive weight gain in the more ideal scenario of being able to plan ahead, Feghali responded that “what we try to do is work with patients so that they get to a status quo of weight at least for 6 months, if there is the possibility of doing that before approaching pregnancy.”

“At that point, I would feel more comfortable, and we know that timing of weight gain makes a big difference,” she added. “I would rather take my chances with later weight gain than early weight gain.”

Ultimately, however, “GLP-1 RA use and pregnancy has become a very common issue and increasingly, we’re going to be having more and more of this conversation with our patients,” Feghali added.

Powe and Feghali had no disclosures to report related to the study.