What is your guidance on GLP-1 agonist use for patients trying to conceive?

Highlights

• Due to a lack of safety data and unknown effects on the fetus, experts unanimously advise discontinuing GLP-1 agonists before a patient attempts to conceive.
• Clinicians recommend a "washout period" of at least two to three months off the medication before patients start trying to get pregnant.
• The long half-life of these drugs is the key reason for the extended washout period, ensuring the medication fully clears the patient's system.
• If a patient has an unplanned pregnancy while on a GLP-1 agonist, the medication should be stopped immediately upon discovery of the pregnancy.
• For pre-conception weight loss, advise patients to use contraception while on GLP-1s and only begin trying to conceive after stopping the medication.

Article

A Consensus on Discontinuation Prior to Conception

Across specialties, there is a clear and unanimous recommendation against the use of GLP-1 receptor agonists in patients actively trying to conceive. The core issue, as highlighted by multiple experts, is the lack of safety data regarding their use during pregnancy. "These are a very new class of drugs, and we don't have much pregnancy information about them," notes Dr. Malavika Prabhu, a maternal-fetal medicine specialist. This sentiment is echoed by endocrinologist Dr. Aviva Cohn, who explains that the primary concern is that "we do not know whether GLP-1 medications are safe in pregnancy, particularly regarding fetal harm." As such, the consistent guidance is to cease administration of these agents before a patient begins attempting to conceive. Dr. Heather Huddleston, a reproductive endocrinologist, puts it succinctly, stating the medications "are contraindicated during pregnancy, so they are not recommended during pregnancy or while trying to conceive."

Defining the Necessary Washout Period

A key consideration for clinicians is the significant washout period required after discontinuing GLP-1 agonists. This is due to the pharmacokinetic properties of the drugs, particularly the long-acting formulations. "These medications, especially when used for weight management, have a long half-life of about a week," explains Dr. Nisha Patel, an internist. "It is important to understand that it takes time for the medications to leave the system."

This lengthy half-life informs the recommended timeline for discontinuation. A consensus appears to center around a two-month washout period. Both Dr. Patel and endocrinologist Dr. Rekha Kumar recommend that individuals stop taking these medications two months before they plan to start trying to conceive. Dr. Prabhu advises stopping "at least a few weeks, and in some cases up to a couple of months, depending on the specific medication." Offering a slightly more conservative timeline, Dr. Cohn states, "I generally recommend a washout period of about three months—stop the medication three months before you try to get pregnant."

"I generally recommend a washout period of about three months—stop the medication three months before you try to get pregnant." Dr. Aviva Cohn

A Structured Approach to Preconception Counseling

For patients of reproductive potential, proactive counseling is paramount. Dr. Huddleston outlines a practical framework for patients using GLP-1 agonists for weight management: "It is a good idea to set a timeframe to work on that goal and use contraception during that period. Once they reach a weight they feel is at or near their goal, they should stop the GLP-1 agonist medication and then begin trying to conceive." This structured approach allows patients to achieve their weight management objectives without incurring fetal risk. For patients with type 2 diabetes, the strategy involves a managed transition. Dr. Prabhu recommends that these patients be transitioned "to a diabetes regimen that is safer for pregnancy" well in advance of attempting conception.

"If a patient needs to lose weight before attempting pregnancy, it is a good idea to set a timeframe to work on that goal and use contraception during that period." Dr. Heather Huddleston

Managing Inadvertent Exposure During Early Pregnancy

Clinicians may encounter patients who discover they are pregnant while taking a GLP-1 agonist. In this scenario, the guidance is immediate discontinuation. If such a case arises, Dr. Huddleston advises stopping the medication immediately. While this situation is not ideal, it may not necessarily portend a poor outcome. Dr. Patel offers a nuanced clinical observation, stating, "There have been reports of individuals who were on the GLP-1 receptor class of medications, became pregnant without knowing, discontinued the medication, and did not experience any complications themselves or in their fetus." However, she is quick to emphasize, "this is not the current recommendation," reinforcing that planned discontinuation remains the standard of care.

Synthesis of Clinical Guidance

The expert consensus strongly advises against the use of GLP-1 agonists during the preconception period due to unknown risks to the fetus. The guiding principle is proactive discontinuation with a sufficient washout period. Clinicians should advise patients to cease these medications for at least two to three months prior to attempting conception. This requires clear, forward-looking counsel, particularly for patients using these agents for weight loss, for whom contraception is recommended until their weight goals are met and the medication has been stopped. For patients with diabetes, a planned transition to a pregnancy-safe regimen is the appropriate course of action. In cases of inadvertent exposure, immediate cessation of the drug is warranted.