One of the most frequent cautions that drug companies print on the Product Information leaflet that comes with their product says something like, “This medication has not been tested to be safe in pregnant women and should only be used in consultation with a healthcare provider.” It’s important to understand that this statement is not a warning that the drug is dangerous for a pregnant woman or the fetus. Rather, it is a statement that the extensive (and expensive!) testing that drug manufacturers have to conduct to get FDA approval for their product in specific population groups wasn’t undertaken; therefore, the drug has not been approved for use in that group. Besides pregnant women, other groups can require targeted testing, such as children, older people, people with pre-existing conditions, etc.
Why are there so many warnings about drugs not being safe for pregnant women?
This is a common complaint that we hear from customers, and there is a simple answer. When tests of drugs are being conducted on human subjects, they specifically exclude pregnant women (or women who may be trying to become pregnant) from the pool of candidates out of fear that the drug may cause some damage to either the mother or the fetus. This is because, before full testing, not enough is known about the actions of the drug for there to be any level of confidence that it is safe in pregnant women to even allow them to be in the trial. So there’s a rather vicious cycle of cause and effect that’s keeping pregnant women off the list of patients for whom the drug is safe. It can’t be tested on pregnant women, so it can’t be determined whether it’s safe for them, but it can’t be determined that it’s safe because it cannot be tested!
Can doctors still prescribe such drugs if a pregnant patient needs them?
In most cases, if there is enough evidence that the drug is suitable, problem-free, and safe for pregnant women, doctors become more confident that they can prescribe it when it meets the needs of their patients. This is what off-label prescribing is all about. The prescribing healthcare provider is the one person with the ultimate knowledge of the patient’s specific conditions and needs and the suitability of the drug in this particular case. About one-fifth of all prescriptions written in the US every year are for off-label use. That number is constantly growing because newer and more specialized drugs are reaching the pharmacy’s shelves every day. These drugs usually start off targeting a narrow range of conditions and so are only fully safety-checked for them. As the drug becomes more widely used, doctors learn from their own experience and colleagues’ experiences, along with journal articles, that ancillary benefits are being reported for patients with different conditions. If they feel that a patient can benefit from the use of this new drug, they begin to prescribe it off-label.
What is the FDA’s approach to drug safety during pregnancy?
The FDA has strict rules about the size and scope of trials that drug manufacturers must conduct before getting their product endorsed as FDA-approved. Although there’s no special leniency that can be given because of the dilemma of not being able to test whether a drug is safe for pregnant women, the FDA recognizes the problem that comes from drug companies excluding pregnant women from their trials and has created a method called the List of Pregnancy Exposure Registries. These registries are published research studies run by drug manufacturers, universities, hospitals, or researchers that specifically looked at the issue of whether the drug is safe in pregnant women and for the fetus during pregnancy. Prescribing doctors can get valuable information on what the rest of the medical community’s experience with a specific drug has been (the consensus) when it has been used during pregnancy.
What is the consensus about the use of GLP-1 RA diabetic and weight-loss drugs during pregnancy?
We must start by repeating that the FDA’s official position is that drugs based on GLP-1 RA formulas, such as Ozempic and Mounjaro for diabetes and Wegovy for weight loss, are not classified as being tested for safe use during pregnancy. The wording used on the official Wegovy product leaflet sets this out quite clearly- “This medicine should not be used during pregnancy, as its effect on your unborn child is not known.”
It’s important to emphasize once again that the company is not saying that Wegovy has proven to be dangerous and can harm the fetus. It’s simply stating the fact that it hasn’t been tested on pregnant women (and we now know why), so doctors should proceed with caution when prescribing it.
Are GLP-1 drugs for diabetes and weight loss now considered safe in pregnant women?
After Ozempic was released in 2017 for the treatment of diabetes, it became the “drug of choice” for many patients, thanks to its ease of administration (weekly self-injection versus multiple daily injections of insulin) and effectiveness. Shortly after the initial surge in the use of Ozempic for diabetes, there was an explosion in demand for the product when it was shown to have remarkable effects in promoting weight loss. In the initial period of switching existing diabetes patients over to Ozempic or its subsequent rival, Mounjaro, doctors generally didn’t have enough information about whether it was safe for pregnant women, so they mainly tended to stick to the FDA’s guidelines and not prescribe it. As data started to come in from the real-life experiences of the tens of millions of people who had jumped onto the GLP-1 bandwagon, it became increasingly clear that there wasn’t a measurable increase in the rate of pregnancy losses or malformations in the fetuses.
Even better news came from a large study titled “Safety of GLP-1 Receptor Agonists and Other Second-Line Antidiabetics in Early Pregnancy.” One conclusion was that in women with type 2 diabetes treated with GLP-1 receptor agonists, the fetus showed no increased risk of congenital malformations than patients treated with insulin.
Conclusion
GLP-1 receptor agonists (GLP-1 RA) such as Ozempic, Mounjaro, and Wegovy remain an open issue regarding their safety in pregnant women. The lack of clinical trials involving pregnant women means that drug manufacturers cannot get FDA approval to market them as safe in this population. This leads to the requirement to include cautionary statements on product labels. However, this does not automatically imply that these drugs are harmful.
Historically, the FDA requires rigorous multi-level testing to approve medications, and almost automatically, pregnant women are excluded from these trials to avoid risks to themselves and their unborn babies. This exclusion has resulted in limited clinical evidence about the effects of GLP-1 drugs on this population group. Nevertheless, with the widespread use of these medications by millions of people worldwide, a growing body of anecdotal evidence and observational studies suggests that GLP-1 drugs probably do not pose significant risks to pregnant women or their unborn children. For example, a large study showed that fetuses exposed to GLP-1 RA in women with type 2 diabetes did not demonstrate an increased risk of congenital malformations compared to those treated with insulin.
FAQs
Why can’t GLP-1 drugs be tested on pregnant women?
GLP-1 drugs, like most medications, cannot be tested on pregnant women due to the risk of causing harm to the mother or fetus. Clinical trials exclude pregnant women, making it difficult to confirm the safety of these drugs in this population. This creates a cycle where the drug cannot be approved for pregnant women without testing, but testing is not performed due to safety concerns.
Can GLP-1 drugs be prescribed off-label for pregnant women?
Yes, in some cases. If a healthcare provider feels that the benefits of prescribing a GLP-1 drug outweigh the risks, they may prescribe it off-label. Off-label prescribing allows doctors to use medications not officially approved for specific conditions or populations based on their clinical judgment and experience.
What is the FDA’s stance on GLP-1 drugs during pregnancy?
The FDA does not endorse the use of GLP-1 drugs during pregnancy, as they have not been sufficiently tested in this population. However, the FDA has created Pregnancy Exposure Registries, which allow for data collection on drug safety during pregnancy, helping provide more information to healthcare providers and patients.
Are GLP-1 drugs considered safe for pregnant women based on recent studies?
Recent studies, such as the “Safety of GLP-1 Receptor Agonists and Other Second-Line Antidiabetics in Early Pregnancy,” have shown that GLP-1 drugs do not increase the risk of congenital malformations in fetuses when used by women with type 2 diabetes. While these findings are encouraging, they are not yet sufficient to fully endorse the use of GLP-1 drugs during pregnancy.
What is off-label prescribing, and how common is it?
Off-label prescribing refers to the practice of prescribing a medication for a condition, member of a population group, or in a dosage not explicitly approved by the FDA. Although the FDA regulates drugs for specific uses, it does not regulate the practice of medicine, meaning that doctors can legally prescribe medications as they see fit based on their clinical judgment.
Off-label prescribing is widespread in healthcare, particularly when new drugs are introduced or when certain populations, like pregnant women, were excluded from clinical trials. Approximately 20% of all prescriptions in the U.S. are off-label, which is growing as more specialized medications reach the market. For pregnant women, off-label prescribing is often necessary because many medications have not undergone the required testing for FDA approval during pregnancy. In these cases, healthcare providers rely on emerging data, clinical experience, and registries like the FDA’s Pregnancy Exposure Registry to make informed decisions.
Is it dangerous for pregnant women to use GLP-1 drugs unknowingly?
If a woman becomes pregnant while taking a GLP-1 drug, she should consult her healthcare provider immediately. While the data is still inconclusive, and there is no evidence that GLP-1 drugs significantly increase the risk of miscarriage or congenital malformations, discontinuation and alternative treatments may be recommended.
