GLP-1 drugs and their effects on the fetus

The recent surge in weight loss and diabetes drugs has led to an increasing number of individuals relying on these medications to effectively manage their chronic conditions. Among these medications, GLP-1 agonists (glucagon-like peptide-1 agonists) have emerged as a promising class to control weight and diabetes. There are thousands of people (and counting) using these drugs worldwide as they are turning out to be game-changers in the fight against obesity and diabetes. However, questions around their effects on pregnancy persist as little is known about safety for the developing fetus and during the breastfeeding stage. It is crucial for us to delve deeper into the associated risks and to acknowledge that we don’t know much yet. When we don’t know the effects, we tend to error on the side of caution. For now, the recommendation is “Women of childbearing age who are taking GLP-1 drugs and wish to become pregnant, or discover they are pregnant, should stop the medication.”

Bullet points: 

👉🏼GLP-1 drugs are in great demand because of their success with weight loss, diabetes, and behavior changes. Rates of obesity and diabetes continue to rise worldwide increasing the sheer number of people on these medications.

👉🏼The majority of people taking these drugs are women of reproductive age.

👉🏼In general, amongst women of reproductive age, more than half of all pregnancies are unplanned and women find out they are pregnant when the fetus is already developed making it pertinent to discuss usage of any medications and their effects.

👉🏼Their use during pregnancy is still being investigated, and there is a lack of comprehensive studies specifically examining GLP-1 drugs in pregnant women.

👉🏼Given lack of data and studies, it is hard to guide women about what to do when they are taking GLP-1 drugs and the inherent risks to a developing fetus. This makes it more urgent to understand GLP-1 drug effects on pregnancy and to have conversations about the risks involved.

👉🏼Until we are certain there is little risk to the fetus, the recommendation is to stop taking the drugs during preconception or when a pregnancy is confirmed. The manufacturers recommend being off the drugs for two months before conceiving.

👉🏼Until we know more, we must consider recommending prevention of pregnancy while taking GLP-1 drugs.

Go Deeper:

More than 1 billion people worldwide are obese – 650 million adults, 340 million adolescents and 39 million children.

The impact can’t be understated. Health Impact: Obesity is associated with numerous health problems, including heart disease, stroke, type 2 diabetes, and certain types of cancer. These are some of the leading causes of preventable, premature death. Economic Impact: The estimated annual medical cost of obesity in the United States was $147 billion in 2008 US dollars. The medical costs for people who have obesity were $1,429 higher than those of normal weight. Working towards a healthier population means working towards finding solutions for obesity and chronic diseases.

What are GLP-1 drugs?

GLP-1 is a hormone in the body that is released into the blood after eating. It increases insulin secretion (which lowers blood glucose levels), reduces glucagon secretion (which also helps lower blood sugar), and slows stomach emptying. This slowing of stomach emptying leads to a feeling of fullness after meals, which can make you not want to eat, leading to weight loss. Because of these effects, GLP-1 drugs are often used in the treatment of conditions like obesity and type 2 diabetes and have proven to have some amazing outcomes.

Most people tolerate GLP-1 drugs well, though the most common side effects may include stomach upset, nausea, dizziness, fatigue, and headaches.

We don’t have studies on pregnant humans, why?

There are no studies in pregnant women because drug testing in pregnant women is a complex and sensitive issue due to ethical concerns around the potential risks to both the mother and the developing fetus.

Here are some reasons why this kind of research is challenging and why we lack comprehensive data from human studies:

• Ethical considerations. Potential harm to the fetus.
• Informed consent. If you don’t know the risks, how do you expect someone to consent?
• Bodily changes during pregnancy are not the same when you are not pregnant. So, we’re not comparing apples to apples.

Because of these challenges, much of what is known about drug safety in pregnancy comes from animal studies, observational studies in humans (where the effects of drugs are observed in pregnant women who have taken the drug for medical reasons), and reports of outcomes in certain case studies (random one-offs of people who took the medications and then we report the results).

Due to these issues, pregnant women and their providers often have to make decisions based on incomplete information and GLP-1 drugs are no different. The Drug Approval Process through the FDA takes years and is vigorous.

What do pregnant animal studies show?

There is very little data on this topic. Some say there is no problem with the fetus, while others have shown defects. Here are some studies that have documented their outcomes. Animal studies usually use very high doses of medications, sometimes way more than would ever be given to a human.

1. In a study named “Preclinical pharmacology and safety of liraglutide,” researchers saw skeletal abnormalities, reduced fetal growth, and increased miscarriages in animals.
2. For another GLP-1 agonist, semaglutide, similar findings have been reported. In animal reproduction studies, semaglutide led to structural abnormalities, including malformations of the limbs and spine. There was also evidence of fetal growth restriction and increased fetal death.
3. A study published in the journal Reproductive Toxicology in 2016 investigated the effects of liraglutide, a GLP-1 agonist, on pregnant rats. The study found that liraglutide did not significantly affect maternal body weight, fetal weight, or fetal development parameters.
4. In the journal Birth Defects Research in 2018, the effects of exenatide were examined, another GLP-1 agonist, on pregnant mice. The study showed that high doses of exenatide caused maternal weight loss and reduced fetal weight, but no major structural abnormalities were observed in the fetuses.
5. A study published in the journal Diabetes, Obesity and Metabolism in 2020 investigated the effects of semaglutide specifically in pregnant rats. The study found that semaglutide treatment resulted in reduced maternal food intake and body weight gain, as well as reduced fetal weight and crown-rump length. However, no major malformations or adverse effects on fetal organ development were observed.

Don’t you have anything on humans?

Human case studies on GLP-1 agonists involve published articles about specific patients’ experiences and outcomes. The person just happened to be on the medication when they got pregnant, and someone wrote an article.

1. Normal pregnancy outcome after first-trimester exposure to liraglutide in a woman with Type 2 diabetes. Diabet Med, 2015 Oct;32(10):e29-30.
   doi: 10.1111/dme.12726.
2. A case of rosiglitazone exposure in the second trimester of pregnancy. Reprod Toxicol, 2005 Mar-Apr;19(4):563-4.doi: 10.1016/j.reprotox.2004.11.003.

So which is it? Good or bad? Bottom line is that we don’t know whether GLP-1 drugs cause problems with pregnancy. We do know that in animals there is some concern about outcomes. The results of these animal studies have implications for how these drugs are classified for use during pregnancy. GLP-1 drugs are Category C pregnancy rating. Category C includes drugs that have shown an adverse effect on the fetus in animals, but there are no adequate and well-controlled studies in humans. Using this information, we deduce, extrapolate to humans. Class C also means that in certain situations, the benefits may warrant use of the drug in pregnant women despite the risks.

It’s important to understand that a Category C designation doesn’t necessarily mean a drug is harmful in human pregnancy. Instead, it means that we don’t have enough information from human studies to say the drug is safe, and the drug has shown some risk in animals. In general terms — use with caution and talk to your doctor.

What is the possible mechanism of harm?

We’re not sure what causes harm to the fetus. Could it be the weight loss or insufficient food, the drug itself, impaired blood flow to the placenta, or a lack of nutrients for the fetus to develop vital organs? It will take years to figure this out. Organs develop in the first few weeks of pregnancy during a time when most women don’t even know they are pregnant. This is a very important factor when considering drugs with unknown fetal effects.

GLP-1 drug manufacturer guidelines:

Wegovy®: Wegovy® may harm your unborn baby. You should stop using Wegovy® 2 months before you plan to become pregnant and are breastfeeding or plan to breastfeed. It is not known if Wegovy® passes into your breast milk.

Ozempic®: It is not known if Ozempic® will harm your unborn baby or passes into your breast milk. You should stop using Ozempic® 2 months before you plan to become pregnant.

What’s next?

Given what we know, most doctors will now be advising their patients who are planning on getting pregnant or are pregnant to stop the GLP-1 medications.

This recommendation is primarily based on lack of sufficient data regarding the effects of these medications on fetal development and maternal health during pregnancy. Most of us will now be asking patients to be on some sort of birth control to prevent unplanned pregnancies while taking GLP-1 medications as most organ development happens before the woman knows she’s pregnant.

Even though there is no consensus yet, there is background chatter that most people will be on GLP-1 medications lifelong. In those situations, women who are planning to get pregnant will have to come off for two months prior to pregnancy, get pregnant, deliver, and then decide when to get back on them.

As for the issue of breastfeeding, there’s no data on that either and we’ll save that for another post when we know more.

The Final Word 🔄

The most annoying thing about practicing medicine is the “maybes” and “possibles”. This is exactly one of the reasons I went into medicine – the dynamic nature of medical knowledge, the not knowing, the minute-by-minute changes of what we understand and recommend leads to “maybe this will work” or “we think this is what happened”. Even if I spent 24 hours a day reading and learning, I wouldn’t even scratch the surface of medical knowledge. This is both frustrating and exhilarating.

Time will tell if women should stay on these drugs while attempting pregnancy and throughout the pregnancy. My guess is that they will stay on it until they get pregnant and then have to come off for the duration of the pregnancy. These drugs are definitely a game-changer and hopefully will help millions of people with chronic diseases.

We don’t know much about GLP-1 drugs and their effects on the fetus. We do know more than we did 2 years ago, and I bet, we’ll know more in 5 years. When we are frustrated by lack of strict guidelines and recommendations, remember that the practice of medicine is dynamic – constant change is the only guarantee.

My most famous quote as a doctor is “Ask me later, I’ll know more next year”.