The dangers of Semaglutide ignorance
The dangers of Semaglutide ignorance
As people turn to more affordable, off-brand Semaglutide formulations clinicians are raising concerns over adverse events from overdosed medications.
Edit 8.25.2024: A link to the late July FDA report on compounded Semaglutide overdosing was not included in the initial publication. The link is now included below.
A few days ago I came across an interesting op-ed published in The Hill:
There’s a few problems with the headline, but the premise here is something that has been commented on several times in the mainstream press.
That is, the limited supply of Ozempic/Wegovy has not been able to keep up with the demand which has resulted in people turning to compounded versions of these brand-name medications.
Now, if you are like me the phrase “compounded version/medication” would sound confusing. Personally, I would take compounded to refer to a medication that is altered through the addition of another medication, as in a compounded version of Semaglutide would just be Semaglutide plus some other additional medications.
It doesn’t help that most definitions of compounded drugs are as ambiguous as the name’s implications, as one can see from this USA Today article that defines compounded Semaglutide the following way:
When there is a shortage of FDA-approved, brand-name medication – like with GLP-1 drugs Ozempic and Wegovy – the FDA says it allows compounding pharmacies to make alternative medications that are "essentially a copy" of the brand-name drug with the same active ingredient. In this case, it's semaglutide, an appetite suppressant.
The FDA defines drug compounding the following way:
Compounding is generally a practice in which a licensed pharmacist, a licensed physician, or, in the case of an outsourcing facility, a person under the supervision of a licensed pharmacist, combines, mixes, or alters ingredients of a drug to create a medication tailored to the needs of an individual patient. Although compounded drugs can serve an important medical need for certain patients, they also present a riskExternal Link Disclaimer to patients.
If this still seems confusing we can break it down the following way:
When prescribed a brand-named medication such as Ozempic you are being provided an active ingredient. The active ingredient is the agent intended to induce a pharmacological effect. In this case, the active ingredient in Ozempic is Semaglutide. However, other agents are also included into the medication, including the solution, agents that inhibit Semaglutide metabolism, and other factors that may increase the bioavailability of the medication such as Novo Nordisk’s inclusion of the compound sodium N-[8-(2-hydroxybenzoyl) aminocaprylate], or SNAC in their GLP-1 RA medications. This is all wrapped up in a specific method of administration such as an injectable pen.
Thus, when we talk about Ozempic we are talking about everything that comprises Ozempic from the active ingredient to every other agent used and the method in which the drug is administered.
So when you hear of people talking about limited supplies of Ozempic or Wegovy it does not necessarily mean that the active agent Semaglutide is in limited supply. It refers to the fact that the brand-named product, with all of its other specific ingredients and method of administration, is in short supply. Semaglutide may be aplenty, but the product Ozempic is not available.
Thus, this shortage of brand-named products has led to many online companies, clinicians, and pharmacists to turn to other means of formulating a usable drug which includes Semaglutide, resulting in many compounded versions flooding the market.
This is where many concerns have been raised regarding these medications, as highlighted by Solomon:
Recently, the FDA issued warnings about compounded versions of semaglutide, the active ingredient in drugs such as Ozempic, Wegovy and Rybelsus, highlighting a big problem: People are using these powerful drugs without enough medical supervision, setting the stage for potential medical malpractice.
The FDA’s warnings aren’t about the agency’s approved versions of semaglutide, which come in handy pre-filled injection pens or oral tablets. The trouble lies with the less expensive compounded versions that are flooding the market. These are not held to the same strict standards, making them significantly riskier.
Essentially, the world of compounded Semaglutide is akin to the wild west where formulations of these drugs is up to the discretion of whichever party the medication is being sourced from. That is, one website may formulate their compounded Semaglutide in a different manner than another. It may contain different ingredients, and in fact can even be administered differently as some sources provide a syringe and vial of compounded Semaglutide in which to administer the drug.
Even more concerning is that dosing of compounded Semaglutide may differ between sources.
For instance, note that Novo Nordisk uses fix-dosed pens:
These pens are designed to contain a specific volume of the drug with a specific concentration of Semaglutide.
These pens are intended to administer consistent amounts of Semaglutide, so that when a patient uses these pens they can do so with the assumption that whichever amount of Semaglutide they are administering to themselves is done with a fixed volume of a fixed concentration.
A bit redundant, but it’s important to emphasize that there is (hopefully) a degree of consistency when using these brand-named medications. One would hope that one Ozempic pen won’t differ too much from another.
However, the same can’t be said when one obtains compounded Semaglutide. Because concentrations and method of administration may differ between sources more due diligence is needed by patients, doctors, and pharmacists to ensure proper dosing is happening.
Unfortunately, this due diligence doesn’t appear to be occurring. In late July the FDA released a report with respect to adverse events from compounded Semaglutide, allegedly from patients overdosing themselves due to lack of knowledge on how to administer their compounded Semaglutide:
FDA has received reports of adverse events, some requiring hospitalization, that may be related to overdoses due to dosing errors associated with compounded semaglutide injectable products. Dosing errors have resulted from patients measuring and self-administering incorrect doses of the drug and health care providers miscalculating doses of the drug.
FDA encourages patients to talk with their health care provider or compounder about how to measure and administer the intended dose of compounded semaglutide.
Many of the patients who received vials of compounded semaglutide lacked experience with self-injections, according to the adverse event reports. Unfamiliarity with withdrawing medication from a vial into a syringe and coupled with confusion between different units of measurement (e.g., milliliters, milligrams and “units”) may have contributed to dosing errors.
Even worse, some of these instructions for dosing were ambiguous, with the FDA noting that some individuals were told to administer “5 units” of their compounded Semaglutide via a syringe. Most patients could not determine what the “5 units” was in reference to, resulting in patient dosing that was 5-20 times above the intended dose:
The majority of the reports described patients mistakenly drawing up more than the prescribed dose from a multiple-dose vial during self-administration. In these instances, patients administered five to 20 times more than the intended dose of semaglutide. Most of the reports indicated that patients were unfamiliar with how to measure the intended dose using a syringe.
In several reports, patients were instructed to use a U-100 (1 milliliter) insulin syringe to draw small doses, such as a 5-unit (0.05 milliliter) dose, from a multiple-dose vial.
As depicted in the figure below, these patients were directed to administer 5 units from a vial. However, these patients mistakenly administered 50 units instead.
The FDA goes on to note an instance in which an individual could not find information regarding dosing from his/her telehealth provider, leading him/her to search online for advice on dosing which resulted in administration of compounded Semaglutide 5 times above the intended dose.
The latter case is a very dangerous scenario given the fact that different sources are likely using different concentrations of Semaglutide, so patients can’t reliably conduct their own research online and get proper dosing instructions. It’s also concerning that some of the companies providing compounded Semaglutide don’t seem aware that dosing instructions should be made explicit to patients and doctors.
Even scarier, doctors don’t seem to be spared from dosing miscalculations. The FDA goes on to report instances in which healthcare providers gave patients wrong dosing instructions leading to adverse events:
Essentially, this is a problem from all sides. Whether telehealth companies, doctors, or patients, many people seem to be incorrectly prescribing, informing, or administering these compounded Semaglutide medications.
Even worse, there’s a large financial incentive structure now in place to administer even more of these medications. As more people turn to these weight-loss medications there should be a growing concern that accidental overdosing may become far more pervasive.
Doctors and telehealth providers may also encourage patients take these medications due to the growing financial incentive to do so, even if it means causing undue harm to patients through ignorance and lack of due diligence.
In response, Solomon believes that we are likely to see medical malpractice lawsuits coming in the near future:
What we’re going to see — and I’ve been predicting this since Ozempic use became prevalent for weight loss — is for Ozempic and medical malpractice to soon intersect far, far more.
Here, we enter the world of medical malpractice, in which a healthcare provider deviates from the standard of care, harming the patient. In the case of compounded semaglutide, several factors come into play in a potential medical malpractice claim, including unclear instructions from healthcare providers, lack of supervision and miscalculations by providers.
Healthcare providers always need to ensure patients understand how to use their medications correctly. When patients feel a need to turn to the internet for dosing instructions, it indicates that providers failed to give clear guidance.
It’s no secret that letting patients self-administer potent drugs without supervision is risky. The many dosage errors show the dangers of this practice. Providers should either give pre-measured doses or ensure that patients know how to measure doses accurately. Instances of providers miscalculating doses shows a lack of diligence and care.
As of now several lawsuits have been filed against Novo Nordisk with respect to adverse events, so it wouldn’t come as a surprise if compounded Semaglutide manufacturers and prescribes face some lawsuits themselves, especially given the lack of due diligence and instruction for patients.
This also raises some serious questions regarding some of the adverse events reported to the FDA, as well as studies which are looking into these adverse events. In some cases it’s possible that researchers may be conflating brand-named GLP-1 RA products which contain fixed-doses of Semaglutide with compounded Semaglutide of which doses is unknown. Who’s to say that many of the adverse events being described are of compounded Semaglutide? If so, then that may suggest that some of these adverse events may just be a consequence of extreme overdosing rather than an issue related to Semaglutide’s pharmacological profile.
Now, Solomon’s response to these current issues is to encourage greater government oversight and regulation on these compounds:
The FDA’s warnings about compounded semaglutide are a step in the right direction, but only if they lead to far more robust regulatory measures. This could include stricter controls on the availability of compounded semaglutide products and more stringent guidelines for telemedicine providers who prescribe these drugs.
It doesn’t help that Solomon’s headline seems to target Ozempic when the real problem seems to be directed towards compounded Semaglutide. After all, there’s an argument to be made that FDA-approved medications are likely to be more regulated than other products on the market, although the past few years have shown that regulatory oversight may not mean much, and may be a way to create the illusion of a drug’s safety and efficacy.
I personally don’t have an answer to this situation, but what I can say is that this is a clear example of the ignorance that pervades healthcare and medicine, and a pervasive epidemic of relying on trust in authority instead of doing your own research.
As more people continue to seek out these medications there’s a greater need for people to ask for transparency and explicit instructions. Ask your healthcare provider for clear instructions on how to take these medications, clear instructions on concentration and dosing, and clear instructions on what adverse events to look out for.
Doctors need to do their own due diligence and ensure the safety of patients, making sure that if they are prescribing these compounded Semaglutide products that they are well-informed regarding the source and the formulation of these products.
Patients must also be wary of doctors and telehealth medicine providers who are entering into this realm of business in order to make a quick buck. It seems that every day a new company or business comes out offering compounded Semaglutide on the cheap. There’s a question if some of these companies are even offering Semaglutide in their products, and unless patients stay vigilant they can be easily harmed by people who put profit over safety.
Be aware of what you put into your body, where that medication is sourced, and whether you are being provided accurate information regarding how to take your medicine and what adverse events to look out for. I think this speaks to a greater issue where many patients seem ignorant as a whole of their very own health.
In a world of uncertainty we need more people to be arbiters of their own health and become their own informed patient advocates.
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