Share on Pinterest- Overdoses related to compounded forms of semaglutide (Ozempic) and other GLP-1 drugs are on the rise.
- The FDA warns that incorrect dosing is common when patients use unapproved formulations.
- Signs of a GLP-1 overdose include extreme diarrhea and vomiting and may require hospitalization.
More people are overdosing on “do-it-yourself” Ozempic as cost and accessibility drive patients to compounded drugs.
Calls to poison control centers about overdoses related to GLP-1 drugs, which includes the blockbuster diabetes and obesity drugs semaglutide (Wegovy and Ozempic) and tirzepatide (Mounjaro and Zepbound), continue to rise.
The apparent culprit: compounded formulations of the popular drugs that, rather than being administered through a pre-measured pen, require the patient to properly dose and inject with a syringe and vial.
Compounded drugs are legal, but not FDA-approved medicines and they may contain different ingredients. When there are drug shortages, compounded versions can help to fill the gap.
There have been 159 calls to poison control centers involving GLP-1s in 2024, compared to just 32 in 2023, the New York Times reported this month. Overdose and misuse of compounded semaglutide has become so prominent that the FDA issued an alert last month warning doctors and consumers about the risks.
In the alert, the FDA acknowledged receiving reports of adverse events, some requiring hospitalization.
Reported symptoms of semaglutide overdose include:
- nausea
- vomiting
- abdominal pain
- headache
The majority of those reports involved dosing errors. In some cases, patients reported administering 5 to 20 times more than the intended dose.
Despite the risks involved in using compounded drugs, healthcare providers acknowledge that they address an unmet need for patients who either cannot access or afford these potentially lifesaving drugs through appropriate channels.
The number of “Ozempic overdoses” continues to grow
“We’re just continuing to see an increase in these calls. And I think what’s important to know is that we’re not just getting calls about compounded products. We’re getting calls about the manufactured FDA-approved products as well,” Joseph Lambson, PharmD, Director of the New Mexico Poison and Drug Information Center, and an Assistant Professor at the University of New Mexico College of Pharmacy, told Healthline.
In 2023, Lambson authored a case report in which he detailed a series of semaglutide overdoses reported to the Utah Poison Control Center. Two patients in that report had self-administered doses ten times higher than intended.
Patients drawing up and administering their own doses may lack the appropriate instruction and knowledge to do so accurately. Additionally, anecdotes of mistaken dose units are also frequent.
FDA-approved semaglutide products use milligrams as their unit of measure. However, patients who self-administer may accidentally use milliliters.
“I’ve had patients come to me after they’ve been on compounded semaglutide, and they would tell me what dose they’re taking and it doesn’t make sense,” Beverly Tchang, MD, an endocrinologist, Spokesperson for the Obesity Society, and Assistant Professor of clinical medicine at Weill Cornell Medicine, told Healthline.
“We think about doses in milligrams. Those are the evidence-based doses that were used in clinical trials. When a patient comes to me using compounded semaglutide, they’ll tell me that they use 50 units. I have no idea what dose that is,” she said.
Weighing the risks of using compounded GLP-1 drugs
The popularity and outsized demand for GLP-1 drugs has led to both national and global shortages, as drug companies struggle to keep up production.
Those shortages, combined with a monthly price tag that can be $1,000 or more per month, have led some patients to seek out other alternatives for their prescriptions.
For some, making the decision between not having their medication or taking a compounded version is no choice at all. That conundrum is something that healthcare providers have increasingly grappled with as well.
“When compounded options were emerging, I think all of us were very much surprised and had a visceral reaction like that’s not a good idea,” said Tchang.
However, her stance has shifted over time.
“I do consider it more of a resource now rather than something we should be afraid of. What makes me nervous about it is that it’s just less regulated,” she said.
Caroline Apovian, MD, a Professor of Medicine at Harvard Medical School and the co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, told Healthline she’s seen first-hand how patients have struggled to access their medication.
“In their desperation, they’ve gone to their primary care physician, who has prescribed compounded semaglutide because it ends up being $500 per month instead of $1,000 per month,” she said.
Despite acknowledging the apparent need for compounded drugs, neither Tchang nor Apovian prescribes them at their respective clinics, nor do they recommend them.
“I am not prescribing compounded semaglutide myself because I have not vetted the pharmacy myself, and I do not have the wherewithal to make sure that the patient is injecting properly,” said Apovian. “On the other hand, I’m not going to tell a patient who comes to see me who has been doing well on compounded semaglutide to stop doing it,” she added.
“From a risk-benefit standpoint, the lowest risk is really with your brand name medications. Those are always the first ones that I would offer to my patients if they’re eligible and if they’re accessible,” said Tchang.
But, she added, “There are patients who will never have access to semaglutide, and that is clearly an area of need.”
In apparent response to that reality, Tchang has written a “checklist” that patients can follow to help minimize their risk when seeking out compounded GLP-1s.
Signs of a semaglutide overdose
GLP-1 drugs are associated with potentially serious gastrointestinal side effects. The most common of them include nausea, diarrhea, and vomiting.
However, more serious side effects including pancreatitis and intestinal obstruction (ileus) can occur.
In the case of an overdose, an individual will likely experience more severe forms of these known side effects.
“Even if the substance is real semaglutide, it could cause GI side effects that can lead to hospitalization, abdominal pain, and projectile vomiting,” said Apovian.
“Any patient or user of one of these products who is concerned that they are experiencing an overdose or are having symptoms that are more severe than they expected can call the poison control center at 1-800-222-1222 for immediate and free and confidential help,” said Lambson.
Additionally, the FDA has also requested individuals to report adverse events through their MedWatch program.
The bottom line
Overdoses related to compounded forms of GLP-1 drugs like semaglutide and tirzepatide continue to increase year over year.
The FDA has warned that many of these overdoses appear to be related to incorrect dosing when self-administering with a syringe and vial. FDA-approved versions of these drugs use a pre-filled pen.
Overdose symptoms include extreme diarrhea and vomiting. In some cases, hospitalization has been required.
