Aug. 6, 2024 – The unbridled demand for weight loss drugs has fueled a surge in nontraditional versions, which are created in compounding pharmacies and available online and through cosmetic medical spas and wellness clinics. But compounded versions are placing people at risk of overdose, the FDA has warned, and the situation doesn’t appear to be improving.
Now, new research shows many sites that are offering the weight loss drug semaglutide online without a prescription are scams or potentially selling toxic liquids that do not contain the labeled amount of the drug. The researchers paid between $113 and $360 for a single dose of the products they ordered online. The retail price for a comparable dose (one 0.25-milligram pen of Wegovy) is about $325, and the drug is meant to be taken weekly.
Though several of these drugs, known as GLP-1s, have been approved for weight loss, the FDA warning specifically focused on dosing errors linked to compounded semaglutide products meant to be injected, some so severe that patients landed in the hospital. In one reported case, a lack of clear dosing instructions from a provider – a telemedicine doctor who prescribed the compounded version – led the patient to search the internet for advice. Ultimately, the person took five times the intended dose.
“There’s a variety of concentrations and vial sizes that patients can receive, and they may administer the whole thing, which at times is more than a month’s worth,” explained Masha Yemets, PharmD, a clinical toxicologist at the Maryland Poison Center at the University of Maryland School of Pharmacy. “So, they can do a tenfold or 20-fold or higher dosing error,” she said.
An ‘Almost Over-the-Counter’ Drug in a Prescription Market
Compounding drugs is not illegal; the process is allowed – especially during drug shortages – so long as it meets certain quality control and other requirements in the Federal Food, Drug, and Cosmetic Act.
Currently, Novo Nordisk is the only company in the U.S. with patents for semaglutide, and no FDA-approved generic versions exist. That means that semaglutide that comes from a compounding pharmacy, a cosmetic medical spa, or online is not the genuine article, has not had a thorough review or met quality standards, and might be downright dangerous.
“The issue is that when drugs are compounded (legally and safely), the active pharmaceutical ingredient or API, is coming from an FDA-approved generic manufacturer. Here we have an API that isn’t generic and is not necessarily made the way that Novo makes it. So, we don’t know what the source product is,” said Angela Fitch, MD, chief medical officer of the health care company Knownwell and past president of the Obesity Medicine Association.
“We’ve turned chronic disease management of a serious chronic illness – obesity – into an almost over-the-counter commercial market. But it’s not being regulated or monitored for safety,” she said.
Dosing Errors Are the Main Concern
Approved semaglutide shots for weight loss are dosed in milligrams, have standard concentrations, and currently come only in prefilled pens. In its warning, the FDA said many patients lack experience with self-injection and don't know much about withdrawing medication from a vial.
Most reports have described patients mistakenly drawing up more than the prescribed dose from multiple-dose vials – in some cases, more than 20 times the intended dose – and said patients were often unclear how to measure the intended dose using a syringe.
“Sometimes patients are reporting doses in units, sometimes in milligrams, sometimes in milliliters,” said Joseph Lambson, PharmD, director of the New Mexico Poison & Drug Information Center at University of New Mexico Health in Albuquerque. “It’s often a similar story, where they’ve had a double or tenfold dose. It’s one of the easiest errors to make.”
Ironically, the FDA also noted that the reports they’ve been receiving describe health care providers themselves incorrectly calculating the intended dose during the conversion from milligrams to units or milliliters, further reinforcing how easily mistakes can happen.
But aside from incorrectly measuring doses, Fitch said, “we have actually seen patients taking more medication themselves, increasing the dose faster because they want to get results faster. What they need to understand is to increase the dose gradually. This is not a drug where you can just take the highest doses and be OK; you need to increase it slowly over time.”
Reported side effects are mostly in the digestive system, but some have been significant. Yemets noted that what’s often sending patients to the emergency room is repeated vomiting, and diarrhea that is so severe, they're seeking care to get rehydrated and stop the vomiting.
But this is only the tip of the iceberg.
“There are more serious side effects that correlate to these medications as a whole, things like acute pancreatitis, whether they’re brand-name, commercially available drugs or compounded semaglutide,” she said.
Other side effects reported by FDA include belly pain, fainting, headache, migraine, and gallstones.
The Bigger Picture
Between 2019 and June 30, 2024, calls to poison control centers have increased more than 1,500% and have totaled 3,866 cases of exposure to GLP-1 drugs. This year alone, America’s Poison Centers – a nonprofit network that provides medical advice on poisonings across the U.S. – has received reports of 159 exposures, said Kait Brown, PharmD, clinical managing director. Overall, between Jan. 1, 2023, and June 30, 2024, “82% of these exposures have been associated with a medication error,” she said.
But Brown emphasized that this data is for all GLP-1 drugs and is not just limited to semaglutide or unauthorized formulations, and some patients are having problems with the official, FDA-approved versions of the drugs.
“We’ve had dosing errors ever since these products came to market, since the very beginning of patient use,” said Yemets. “It’s really just at the end of last year where we had a lot of cases with the compounded version that correlated, timeline-wise, with the FDA placing these drugs on the shortage list.”
Bridget Pilloud, a writer based in Washington state and Arizona, said that she’s already had issues with the approved, branded drugs.
“The first week, I was in the doctor’s office, and she showed me how to use the pen, and it seemed pretty straightforward,” she said. “I was confused with the marks, and I didn’t know that I needed to hear the pen click when you turn the dial.”
Ultimately, despite having watched a YouTube video and re-reading the instruction pamphlet, Pilloud phoned her doctor, who reinforced that it was unclear how much drug she had gotten (or not). “The information is not intuitive,” said Pilloud.
Leigh Fazzina, a pharmaceutical marketing executive from the Philadelphia area, also shared that although she visited a reputable, academic clinic and was given a prescription for the FDA-approved drug, she was never shown the actual pens or how to use them. A YouTube tutorial and a call to the drugmaker's 800 number helped her overcome the lack of information and use the pen correctly, but she’s convinced that without her background knowledge, she wouldn’t even know what to do or where to seek information.
“I must have been searching the internet for more than an hour; someone with a health literacy issue might struggle even more,” she said.
“We definitely get calls for the manufactured products,” said Lambson, of the New Mexico Poison & Drug Information Center, who said he is helping with a study to learn the percentage of calls that are about compounded medicines, vs. not, to try to get a sense of their differences in terms of side effects.
“The stories are different; for example, we don’t typically get a tenfold overdose with the manufactured product, but often they are dispensed with the incorrect pen, so patients get a double or fourfold dose,” he said.
How to Stay Safe
It’s essential to understand how to dose these drugs as instructed. “Make sure that you get these medications through a medical practitioner and pharmacy, and that you receive counseling on how to take the medication and what to expect when you do,” advised Lambson. The pharmacist might be able to help patients who are using a compounded version learn important steps, like how far to draw back the syringe or, with the pens, the tabs to pull, buttons to push, and how long to push them, he said.
Finally, if you have any side effects related to use of semaglutide or any other GLP-1 inhibitor, stop right away and call Poison Help at 800-222-1222 to speak with a poison expert, or visit PoisonHelp.org for support and resources.
The FDA also encourages patients to report side effects and medication errors that come with these products to its MedWatch Adverse Event Reporting Program.
