Many Sites Lack Info on Compounded GLP-1 RAs

More than a third of websites that advertise and sell compounded versions of popular drugs for diabetes and weight loss — such as Ozempic and Wegovy — falsely claim the compounded medications have been approved by the Food and Drug Administration (FDA), according to a recent research letter.

Compounded drugs, such as those using the active ingredient in Ozempic and Wegovy (semaglutide) or in Zepbound and Mounjaro (tirzepatide), are not FDA-approved and are not regulated in the same way as FDA-approved medications. Because of that, they come with risks, such as too much or too little active ingredient or contamination, even though they can be legally used in times of drug shortages. Currently, semaglutide is considered by the FDA to be in short supply. Compounded medications may also be used when individual patients have an allergy to a certain dye or a need for a different formulation (such as a liquid instead of a pill).

“One of the major findings was that many of these websites did not disclose that compounded GLP-1 RAs [glucagon-like peptide 1 receptor agonists] are not FDA-approved, and some of them suggested that they are,” said first author Ashwin Chetty, a second-year medical student at Yale School of Medicine, New Haven, Connecticut. “And that is really concerning because that is a core piece of information to understanding what a compounded drug is.”

The cross-sectional study was published in JAMA Health Forum on January 17.

To conduct the study, authors used Google Shopping to search for websites advertising prescriptions for, or the sale of, compounded semaglutide, tirzepatide, and/or liraglutide (the active ingredient in the FDA-approved drug Saxenda). Searches were conducted between July and September 2024.

The authors then reviewed the websites they found and evaluated data on medications sold, location, prices, disclosures of compounding, safety and efficacy claims, and clinician involvement and calculated descriptive statistics.

Ninety-eight websites were identified that sold any GLP-1 RAs, 79 of which sold or prescribed compounded medications. Of those:

• All of them sold compounded semaglutide.
• Fifty-seven (72%) sold compounded tirzepatide.
• Three (3.8%) sold compounded liraglutide.

Other important details:

• Eleven websites (almost 14%) did not disclose that the GLP-1 RAs they sold were compounded.
• Seven (nearly 9%) called compounded medications “generics,” which they are not (a generic drug is approved by the FDA).
• Thirty-four (43%) noted that compounded medications are not FDA-approved.
• Twenty-nine (36.7%) stated or implied that they were FDA-approved.

The study also found that 39 websites (49.4%) failed to report adverse effects, precautions, warnings, and contraindications of compounded GLP-1 RAs, and 32 (40.5%) published a claim of effectiveness that is not present on the label of the FDA-approved brand GLP-1 RA.

For example, some of the websites made unsubstantiated claims, such as that the medications would lead to better sexual function or more hair growth, said study author Alissa Chen, MD, a postdoctoral fellow at Yale School of Medicine in the National Clinician Scholars Program and a primary care doctor at Cornell Scott-Hill Health Center in New Haven, Connecticut.

Nearly all the websites, 78 (98.7%), required some level of clinician involvement to get a prescription.

“This cross-sectional study showed websites that sell compounded GLP-1 RAs often partially informed and sometimes misinformed to potential consumers,” study authors wrote.

Claims of safety and efficacy were not balanced, Chetty told Medscape Medical News, explaining that the websites offered limited safety information on these compounded medications.

“That ultimately gives an incomplete and incorrect picture to patients and consumers,” Chetty said.

“And so that leaves the potential for patients to become misinformed about what they can gain from taking a GLP,” Chen said.

While semaglutide and liraglutide (the active ingredient in Saxenda) are still in short supply, the FDA recently declared the tirzepatide shortage resolved, according to the agency’s drug shortage list.

One of the study’s limitations is that “because we reviewed all information reported on websites, including on subpages and associated blogs, we likely overestimated the amount of information that typical consumers review,” authors wrote.

What Doctors and Patients Need to Know

Chetty said he originally wanted to do the study because the FDA has released announcements about the risks for compounded GLP-1s, including instances of misbranding or incorrect dosing of them.

“But one of the questions that really wasn’t discussed in the FDA announcement or in the popular media articles is: How are these websites talking about compounded GLP ones?” Chetty said.

Because compounded drugs are not FDA-approved, the agency does not verify their effectiveness, safety, or quality. Federal law mandates that advertising of all prescription drugs — compounded medications included — must be truthful, accurate, and not misleading.

Physicians need to be aware that their patients aren’t going to understand the intricacies of what an FDA-approved medication is or isn’t.

“And so helping them understand that, I think, is an important place for physicians to be,” said Chen, who focuses her medical practice on patients with hypertensive disorder and obesity.

Physicians should approach patients with empathy and be open to patients who are seeking out a compounded GLP-1 RA, Chen said. For example, before expressing concerns about potential harms, doctors should ask patients to tell them more about their situation. Many people are seeking out weight loss therapies and want to cure their obesity and be healthy, she said. And they’re trying anything they can to do that. “So, I think physicians really need to be supportive of that goal, even if patients are approaching it from a way that they might not recommend.”

It’s also important for physicians to know if their patients are on a GLP-1 RA that’s been prescribed elsewhere. When physicians see patients who are obese or interested in weight loss, physicians should ask them if they are already using a GLP-1 RA medication, said Chen. “I’m sure many physicians are not aware if their patients are taking these medications.”

It’s important that doctors know if patients are taking these medications (compounded or branded) because they could interact with medications a patient is already on, Chen said.

Another point is the cost. GLP-1 RAs are quite costly, and insurance often doesn’t cover them. Compounded GLP-1 RAs are much cheaper.

Chetty pondered what he would do if he were in a position where he really needed a GLP-1 RA for himself. Would he take a less expensive compounded version? He said he doesn’t know. It comes down to how you manage risk as an individual, he said.

As for patients, “I think if they are interested in taking a compounded GLP-1 RA, they should talk to their healthcare provider about the risks of a GLP first.”

Going forward, Chetty said he would like the FDA to release clear guidelines around marketing of compounded drugs. He hopes that a future study could look into what level of clinician involvement is actually required to obtain compounded semaglutide.

“Relying only on the information provided on these websites is not all the information that you should have to make that decision,” Chetty said.

Joanna Broder is a science and breaking news editor and reporter.