In the face of ongoing shortages of the obesity and diabetes medications known as GLP-1s, patients have resorted to a wide array of sources for the drugs, including medical spas and telehealth sites that prescribe compounded versions of the drugs. But a new paper published in JAMA Network Open highlights one of the riskiest sources of non-branded drugs: illegal online pharmacies that bypass prescription entirely.
Researchers from the University of San Diego and the University of Pécs in Hungary found that semaglutide ordered from these illegal sites contained significantly more of the drug than labeled. One sample also contained signs of potential bacterial contamination during manufacturing.
“It’s just a very, very risky business, going online and buying this product,” said Tim Mackey, a professor of global health at the University of California, San Diego and co-author of the study. “Just because it’s online and it’s accessible and it can be sold without a prescription, does not mean it’s authentic.”
Concern over the safety risks of non-branded versions of popular obesity medications is on the rise — both counterfeit drugs and compounded versions. Last week, the Food and Drug Administration issued an alert about the risks of compounded GLP-1s, citing adverse events like severe vomiting related to dosing errors — some even requiring hospitalization. In May, Australia banned compounded versions of the drugs because of the challenges in ensuring their safety.
America’s Poison Centers reported nearly 5,000 calls about GLP-1 exposures in 2023 — a more than fivefold increase from calls reported in 2019. This year, calls are on track to reach nearly 8,000. Of those calls about exposures, 191 have been explicitly attributed to compounded GLP-1s: 159 this year, and 32 in 2023.
Prescription of the compounded drugs — which are not approved by the FDA or evaluated for safety or effectiveness — is currently enabled by the existing shortages of Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy, both of which have been approved for treating obesity. As long as the branded medications are not readily available, compounding pharmacies can legally manufacture and sell non-branded versions of the drugs.
Non-branded drugs are often sold in vials, and patients must assemble the correct dose themselves using a syringe, increasing the risk of dosing errors. Branded semaglutide approved for obesity, by contrast, is sold in pre-filled pens. Of poison control center calls about compounded GLP-1 exposure, 82% were related to medication errors, according to Kait Brown, clinical managing director of the America’s Poison Centers.
Researchers’ analysis of semaglutide from illegal online pharmacies that allow users to buy the drugs without a prescription point to additional risks.
When researchers searched for no-prescription semaglutide in July 2023, they turned up 134 illegal online pharmacies. They bought semaglutide in 0.25-mg pens or injection vials from six of them. Of those six, only three arrived at their doorstep: Half of the companies tried to scam users out of extra money for what was advertised as Ozempic, demanding hundreds of extra dollars to “clear customs” and complete delivery.
There were safety problems with all three semaglutide vials that did arrive.
All three had far more semaglutide than labeled — between 29% and 39% more, adding to the risk of misdosing the medication. One vial showed signs of unsterile conditions during manufacturing, with elevated levels of endotoxin, a castoff from bacteria, though further testing found no viable bugs in the sample.
“This study shows two very different forms of patient risk,” said Mackey. “One, you just get scammed. Which is not great, but at least you don’t get insulin, or you don’t get a product that could have some contaminants in it. And two, you get something that has too much in it because the counterfeiters want to make sure that you come back for product.”
Mackey and his co-authors acknowledged the small number of doses tested limits their analysis. Still, they concluded, “illegal online pharmacies, which operate without valid licenses and sell medicines like semaglutide without prescription, represent a consumer risk for ineffective and dangerous products.”
“FDA-approved prescription drugs should only be obtained with a valid prescription from a legitimate pharmacy and used under a prescriber’s supervision or based on their direction,” FDA spokesperson Amanda Hils wrote in an email to STAT. “Purchasing prescription drugs from unregulated, unlicensed sources without a prescription is risky and some websites may appear to be legitimate online pharmacies, but they are actually operating illegally and selling medicines that can be dangerous, even deadly.”
Of the three sites from which vials were tested, two have received warning letters from the FDA for selling misbranded and unapproved drugs since the study was conducted. STAT previously reported on patients using these sites, some of which market themselves as laboratory-grade peptide suppliers that sell compounds for research purposes only.
“Despite statements on your product labeling marketing your products as ‘research chemicals only’ and ‘not for human consumption,’ evidence obtained from your website establishes that your products are intended to be drugs for human use,” reads the February warning letter for one of the sites.
That site, along with the third pharmacy whose vials were analyzed in the study, were still up and listing semaglutide for sale as of August 1, though they were both out of stock. One of the scam pharmacies still invokes users, in bold, 50-point font, to “buy Ozempic online without prescription.”
Since the researchers conducted their analysis, the online marketing of non-branded GLP-1s has shifted toward compounding pharmacies with their own set of safety considerations, said Mackey. But “there’s a lot of blurring of the lines, I would say, between compounded pharmacies and finished product and online pharmacies and research grade chemical providers,” he said. “And the last group that needs to try to figure that out is the consumer.”
Physicians have voiced concern over the risks of counterfeit and compounded GLP-1s as patients continue to seek them out in the face of shortages and lack of insurance coverage for the expensive branded medications.
Online sellers who don’t require a prescription “should be an immediate red flag to patients that the seller does not have the patient’s best interest in mind,” said Cate Varney, director of obesity medicine at UVA Health, who discourages patients from using any drug not approved by the FDA. But if they are driven to use prescribed compounded medications, she encourages them to get as much information as possible from the pharmacy about where the medication came from, where it was manufactured, and the license number of that pharmacy. “If they cannot give you that information up front, or they’re weird about giving that, I would avoid any company that would not be transparent about that information,” she said.
The availability of compounded semaglutide may diminish as supply increases of branded drugs including Zepbound and Wegovy. Yesterday, Eli Lilly CEO David Ricks said that the Zepbound shortage will likely come to an end this week, Bloomberg News reported.
For emergency assistance, please call Poison Help at 1.800.222.1222 to speak with a poison expert, or visit PoisonHelp.org for support and resources.
This story has been updated with FDA comment.
