Semaglutide Overdose – What Does It Look Like and Why Is It Happening?

Semaglutide products have been popping up in news headlines recently, and not because of their continued popularity as effective weight loss medications. Data from poison control centers across the country indicates a drastic increase over the past year in calls related to semaglutide overdose — an increase of over 1500% since 2019 according to a CNN report. An increase of that magnitude in such a comparatively short time is enough to draw the notice and concern of both providers and patients. In this article we’ll cover what doses or quantities constitute an overdose of the medication, what kind of reaction it causes in the body and how it is dangerous for patients, and, finally, what are some of the potential reasons for the sudden spike in overdoses. 

Most medications have an identifiable dose, range of doses, or serum level that is considered unsafe or toxic for most patients. However, it is not always so straightforward if the medication has an unusual dosing schedule/frequency (i.e. weekly or monthly or other predefined intervals) or if the medication has pharmacokinetic properties that make it unique. 

Semaglutide overdose is generally considered taking more than what has been prescribed. Based on the available literature, there is no definitive answer for what dose of semaglutide is considered toxic. This isn’t necessarily surprising since it is a once-weekly medication and the dose that a patient needs can vary from anywhere between 0.5mg and 2mg weekly based on their tolerance or needs. For instance, it is reasonable to say a patient who is only able to tolerate a maintenance dose of 0.5mg may experience overdose severity symptoms if they were to take 3 to 4 weeks’ worth of doses (approximately 1.5mg to 2 mg) all at once, while other patients may not experience severe symptoms unless significantly higher amounts were administered. 

The fact that the medication is injectable (meaning it is more rapidly absorbed) and its long half-life in the body (approximately 1 week), is another element that complicates things. There is no direct antidote to semaglutide that will negate or reverse its action in overdose. So, once it is administered it must go through the body’s natural metabolism process. Large quantities of Semaglutide do not damage the body directly or result in the buildup of toxic metabolites like other medications.  However, the large quantity of medication will act on the body in accordance with its mechanism of action and result in an excess of the desired effect. Semaglutide overdose is most likely to lead to hypoglycemia, severe nausea, vomiting, and abdominal cramps. If these symptoms are left untreated or not treated properly, they can be dangerous or even fatal. Learn more about semaglutide pharmacology on this podcast episode.

So far, we’ve covered a few important points. There is no definitive dose that can be classified as an overdose of Semaglutide but anything more than what would be the patient’s normal weekly dose can lead to adverse effects that can vary in severity based on how much excess medication is administered. There is no antidote to reverse the medication’s effects, and once it is administered the body must metabolize it at its own pace to clear it. An excess of this medication can lead to severe hypoglycemia, nausea, vomiting, and abdominal pain among other symptoms, and these symptoms can be dangerous if not treated promptly and properly. 

Why So Many Semaglutide Overdoses?

The next question we’re going to address is why there has been such a dramatic increase in cases of semaglutide overdoses being called into Poison Control. The primary reason that underlies all others, is patient error during administration. These errors can range from accidentally double dosing to administering the wrong quantity of medication. Providers with America’s Poison Centers expressed that many of the calls they receive are these sort of dosing errors.

The once-weekly dosing of injectable Semaglutide can make it easy for a patient to forget when they took it or if they took it, leading to doubling up of doses. While it is important for these patients who accidentally double dose themselves to contact their provider and carefully monitor their symptoms, it does not generally lead to a crisis. 

Then there is the issue of administering the wrong dose. Whenever a medication is self-administered, there is always the risk for error and that risk increases based on the complexity of the steps required. In the case of Ozempic (Semaglutide), the patented pen injector system removes many chances for patient error in dosing. However, it is still possible for a patient to incorrectly dose themselves by dialing the pen’s dosing system too far. This is a particularly prevalent risk in patients who struggle with dexterity or poor eyesight. Novo Nordisk has been made aware of several cases in which a dosing error was made using their pen injector devices so that they can address any problems from their end with the standard prescription product. 

The bigger issue that has become increasingly apparent to Poison Control Centers as well as Novo Nordisk, is the presence of compounded versions of semaglutide products being sold on the market. There is currently no FDA-approved generic form of injectable semaglutide but since the medication went into shortage in early 2022, qualified pharmacies have been able to begin producing compounded versions of the medication. These compounded versions are not sold in a pen injector like Ozempic or Wegovy, but instead in multidose vials where a patient must draw up each individual dose themselves. This is like what we see when patients use vials of insulin rather than insulin pens, and places patients at risk for many of the same errors. It is easy for a patient to draw up too much product or confuse volume measurements such as 0.1mL and 1mL, leading to dangerously high doses being given. The fact that many compounded products are solid in dosages and concentrations that are not FDA-approved further complicates matters. The non-standard dosing in itself can be confusing for a patient but it also presents providers at Poison Control or other acute care settings with the problem of trying to figure out what the correct dose was and exactly how much excess medication the patient received. It is suspected that compounded products are behind a large portion of the calls made to poison control and account for some of the more extreme overdoses. Based on calls made to poison control, some patients have accidentally administered up to 10 to 20 times the standard dose of Semaglutide.

Despite warnings from the FDA, these compounded medications are attractive to many patients because they appear to be a cheaper, more accessible alternative to the prescription product, especially for those patients whose insurance does not cover the cost of Ozempic or Wegovy. They are available from online sellers and even some health spas but just because they are marketed as Semaglutide products does not mean that they are the same as what patients will find in prescription products like Ozempic or Wegovy or that they are dosed in the same way. 

Semaglutide Overdose Management

Finally, what can be done to treat patients who present with semaglutide overdose or other GLP-1 medications? Unfortunately, since there is no antidote to reverse the medication’s effect, acute care providers can only provide supportive care to their patients until the medication has been cleared from the body. It is important in these cases to monitor blood glucose and take measures to prevent hypoglycemia. Fluids should be provided to prevent dehydration caused by vomiting and antinausea medications can be provided to manage the worst of the symptoms. Prolonged hospitalization is generally not needed unless the dose was exceptionally high. 

Healthcare providers like pharmacists can help prevent these types of errors by ensuring that patients are properly counseled and educated on how to use their pen injector devices before administering them at home. If a pharmacy has access to tester pens that can be used to demonstrate the process and allow patients to practice, that is an excellent way to make sure that directions on dosing and administration are clearly understood. We can also make sure that we educate our patients, when necessary, on the risks that are associated with compounded medications and ensure that, if a compounded product is all that is available, extra counseling is provided to make sure that the patient is able to draw up the correct dosage safely and successfully. 

This article was written by Tori McDougald in collaboration with Eric Christianson, PharmD, BCPS, BCGP

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  1. Richard Wagner

    Thank you. Knowledge unshared is wasted. Thankfully you share yours.

    • Mary N, RN, BSN

      Thank you for the clear and timely information. Eric you are literally a trusted voice on pharmacology for me, as I enjoy your podcasts. I am going into my second semester of a psych NP program. I am seeing am seeing information about prescribing semiglutide with some antipsychotics to lower rates of metabolic syndrome, so am keeping a close eye on them

  2. Tommy

    You’re right Rich, knowledge if un-shared is wasted…


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Written By Eric Christianson

December 17, 2023

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