As GLP-1 weight-loss drugs become more widely used, more people are running into a question the research has not fully answered: What happens if you are taking one and want to get pregnant?
A new review and set of expert recommendations published in Obesity Reviews offers some guidance. The authors say GLP-1-based medications should not be intentionally continued during pregnancy. At the same time, the human evidence available so far has not found a higher rate of major birth defects among people who were exposed around conception or early in pregnancy.
That finding may be reassuring for someone who discovers they are pregnant after taking one of these medications. But it does not mean the drugs have been proven safe throughout pregnancy.
“However, for those who may have used the injections without realising they were pregnant, the current data show no increased risk for congenital anomalies following exposure in early pregnancy – which we hope will be reassuring,” said lead author Kate Maslin of the University of Plymouth.
The international research team reviewed 34 studies involving medications including semaglutide, liraglutide, dulaglutide, exenatide and tirzepatide. Most of the evidence involved use before pregnancy or accidental exposure early in pregnancy.
There were still major gaps.
The researchers found direct evidence for only 18 of the 32 questions they set out to answer. For nearly 44%, there were no relevant human studies. In those areas, the recommendations are based on expert consensus rather than strong clinical evidence.
One of the clearest messages concerns accidental exposure in early pregnancy.
Across the studies included in the review, researchers did not find a higher rate of major birth defects among pregnancies exposed to GLP-1-based medications. Two of the larger studies included 938 and 163 exposed pregnancies and found rates similar to those seen in pregnancies among people using insulin for type 2 diabetes.
But very few people continued the medications throughout pregnancy. That means researchers still do not know enough about longer exposure to call it safe.
For that reason, the authors recommend stopping the medication once pregnancy is confirmed if it has not already been stopped.
When to stop before trying to conceive is less certain.
Manufacturers generally recommend stopping some of the longer-lasting drugs several weeks before pregnancy, but the review found no strong evidence showing exactly how long people should wait. The authors recommend discussing pregnancy plans with a health care professional rather than assuming the same timeline applies to everyone.
Birth control is another important part of the guidance.
The authors recommend reliable contraception for people who could become pregnant while using these medications. They call for extra caution with tirzepatide because it can make oral birth control less reliable. The guidance recommends using a non-oral form of contraception with tirzepatide.
The review also highlights something that can easily get lost in conversations about weight-loss drugs: nutrition.
GLP-1 medications can reduce appetite enough that some people eat substantially less. That can make it harder to get enough protein, vitamins and minerals, which may be especially important for anyone planning a pregnancy.
Surprisingly, the researchers found no studies specifically looking at vitamin or mineral status in women taking these drugs before conception, during pregnancy or after giving birth.
The authors therefore recommend nutrition counseling for people of reproductive age using GLP-1-based medications. Their guidance emphasizes nutrient-dense foods, enough protein and fiber, good hydration and standard preconception advice such as taking folic acid and vitamin D when appropriate.
Fertility is another area where the evidence is still developing.
Some studies suggest GLP-1-based medications may improve menstrual regularity, ovulation or pregnancy rates in women with polycystic ovary syndrome, or PCOS. But much of that research involved older medications and, in some cases, treatment with metformin at the same time.
That makes it hard to know whether the improvement came from the medication itself, from weight loss, from better blood sugar control or from a combination of factors.
The review also does not establish GLP-1 drugs as fertility treatments.
Another unanswered question is what happens after someone stops the medication to become pregnant.
Weight regain is common after GLP-1 treatment ends in the general population. Some newer research suggests that people who stop before or early in pregnancy may also gain more weight during pregnancy, but the evidence is not yet clear enough to know how often that happens or what it means for pregnancy outcomes.
The authors therefore recommend keeping an eye on weight gain during pregnancy after treatment stops.
Breastfeeding is even less studied.
The review found only one small human study of semaglutide during breastfeeding. It included eight women and did not detect the medication in breast milk samples. No problems with infant growth were reported, but the study was small and did not examine milk production or milk composition.
That is not enough evidence to say GLP-1 medications are broadly safe during breastfeeding.
The new guidance recommends making those decisions individually, taking into account breastfeeding goals, the possible benefits of restarting treatment and the lack of long-term safety data for infants. If a GLP-1 medication is used while breastfeeding, the authors recommend monitoring the baby’s growth and development along with the mother’s nutritional status.
Researchers also know very little about longer-term effects.
There are no human studies showing what happens to children years after exposure during pregnancy. Scientists also do not yet know the best time to restart treatment after giving birth or whether different GLP-1 medications carry different risks before, during and after pregnancy.
“As well as providing evidence for guidelines, the main takeaway from this current study is that much more research needs to be done to understand how weight loss injections affect all aspects of reproductive health,” Maslin said.
The review received no external funding. Several authors reported financial relationships outside this work with pharmaceutical or medical technology companies, including Novo Nordisk, Eli Lilly, Amgen, Pfizer and AstraZeneca.