FDA Investigates Potential Side Effects of GLP-1 Drugs: Hair Loss and Suicidal Ideation

The Food and Drug Administration (FDA) is currently examining widely used drugs such as Ozempic and Wegovy due to potential associations with suicidal ideation, hair loss, and aspiration.

Adverse event reports related to Glucagon-like peptide-1 (GLP-1) receptor agonist drugs have been filed with the FDA’s Adverse Event Reporting System (FAERS). These drugs are currently part of an FDA review list, last updated on January 2.

Among the GLP-1 drugs under consideration are newer ones such as Wegovy and Mounjaro, as well as older type 2 diabetes drugs like Byetta, first approved in 2005.

At the moment, the FDA is only "assessing the need for regulatory action". Drug manufacturers have not yet been asked to take any steps, such as updating their package label warnings.

This examination comes around six months after the European Medicines Agency (EMA) stated that it would be reviewing a possible link between GLP-1 drugs and suicidal ideation, after approximately 150 reports of the issue.

The investigation was initially expected to conclude in November, but the EMA committee recently submitted "further lists of questions to be addressed" to companies that market GLP-1 drugs. The committee is scheduled to revisit the issue in April.

In addition, a study published on January 5 examined a possible association between semaglutide—also known as Ozempic and Wegovy—and suicidal ideation. It was found that these drugs did not have a higher risk of suicidal thoughts compared to other type 2 diabetes and weight loss drugs.

As health officials and researchers continue to explore GLP-1 drugs and any previously unlisted side effects, experts concur that the review should not cause alarm.

"I believe [the review is] appropriate, that’s their regulatory goal: to ensure safety," said Holly Lofton, MD, NYU Langone Health's medical weight management program director.

Although the FDA's adverse reporting system identified alopecia (hair loss), aspiration, and suicidal ideation, it does not necessarily prove that these side effects were caused by the drugs.

However, the FAERS review system does allow the FDA to monitor any emerging safety issues, particularly when a drug sees widespread public use.

“These side effects were not observed in clinical trials, but those only account for about 3,000 patients on both sides. In the live market, we are dealing with millions of patients,”, Ebne Rafi, PharmD, specialist in clinical pharmacy at University Hospitals' Diabetes and Obesity Center in Cleveland, said.

This review is the FDA “fulfilling its duty,” he explained.

Even though there is no confirmed link between GLP-1 drugs and the three side effects identified by the FDA, previous studies have suggested associations.

Suicidal ideation is historically associated with weight loss drugs. Some weight loss drugs have even been withdrawn from the market due to an elevated suicide risk, Lofton said. Weight loss drugs' impact on the central nervous system is likely to contribute to this increased risk, according to Rafi.

It's worth noting that suicidal ideation is listed as a warning in the prescribing information for Wegovy.

Hair loss and weight loss are also connected. “Alopecia is one of the newer side effects under investigation,” Rafi mentioned. “Rapid weight loss could create hormonal imbalances and changes in a particular type of collagen which may lead to hair loss in some cases.”

This effect has been observed in individuals who have experienced significant weight loss after undergoing sleeve gastrectomy.

The relationship between GLP-1 drugs and pulmonary aspiration (accidental inhalation of material that ends up in the lungs) is less clear.

The Canadian Journal of Anesthesia warned in July 2023 about patients inadvertently inhaling gastric contents during surgery because their stomachs cannot fully empty. There's limited research on the potential link between GLP-1 drugs and the accidental ingestion of food into the airway.

For now, the FDA is only "assessing the need for regulatory action", so the future changes in the usage of these drugs, if any, remain uncertain.

This action could include “updating a product’s labeling information, restricting the use of the drug, communicating new safety information to the public, or, in rare cases, removing a product from the market.”

This latter option is highly unlikely in the case of GLP-1 drugs, experts agreed. Even if there is some causal link that’s shown to exist between these side effects and GLP-1 drugs, that wouldn’t necessarily warrant making it unavailable, Rafi explained.

“For example, chemical antidepressant medications have [suicidal ideation risk] as a major warning. A majority of anti-seizure medications also,” he said. “And these medications have been on the market for years and years.”

If anything, the FDA may ask companies to update their labels to include these possible side effects, experts said. This just happened in October—the FDA added a gastrointestinal side effect, ileus, to Ozempic’s label.

As for why these reviews are cropping up now, Lofton said it’s largely because of the “sheer mass of people who are taking some form of these drugs.” In other words, the number of adverse events is growing as the number of people taking the drug also increases. 

Though the FDA review is important, there’s no need for people to be “stressing out over it,” especially when, for now, there’s no proven link between GLP-1 drugs and alopecia, aspiration, or suicidal ideation, said Rafi. 

This is especially true for people who have already taken the medication and are seeing good results. 

“I have many patients who come in and they’ve been on these drugs for years with me, and they say, ‘I’m so worried about ileus.’ And I say, ‘Well, did you get ileus?’ ‘No, I didn’t get it.’ ‘Okay, well, then don’t worry,’” Lofton said.

However, patients or anyone considering taking Ozempic, Mounjaro, or a related drug should be aware of any potential risks and should be on the lookout for these or other side effects. This is especially true since every person’s experience on the medication is different, she added.

“As providers, we need to make sure to make patients aware of potential side effects, especially the serious ones,” said Lofton, “and then follow up with patients and make sure nothing untoward is putting them in a state where they have more risk than benefit.”