Over the past few years, weight loss medications have become very popular, thanks in part to a class of drugs called glucagon-like peptide-1 receptor agonists (GLP-1RAs). GLP-1RAs like semaglutide (Wegovy) and tirzepatide (Zepbound) have contributed to a significant increase in prescription spending in the U.S., but their growing popularity has also led to medication shortages. Many people have struggled to access these medications due to supply issues, high prices, and limited insurance coverage. In response to these challenges, compounded versions of GLP-1RAs have become more widely used. These products may be more accessible and, in some cases, cheaper for people facing insurance-related barriers. However, while compounded GLP-1RAs improve access, they come with important safety risks to consider.
What is a compounded medication?
The FDA defines “traditional” pharmacy compounding as “combining, mixing, or altering ingredients to create a customized medication for an individual patient based on a licensed practitioner’s prescription.” Compounded drugs use FDA-approved ingredients, but the customized medication itself is not FDA-approved. This means the FDA does not specifically review the safety, effectiveness, or quality of compounded medications before they are given to patients.
Customizing medications can offer several benefits, such as:
- Providing alternative dosage forms (e.g., liquids for patients who have trouble swallowing)
- Re-flavoring medications to improve taste
- Removing allergens found in commercially manufactured products
- Creating specific doses that are not commercially available
Community pharmacies vary in their ability to perform basic compounding based on their space and materials. In most cases, medications that require compounding are sent to pharmacies that specialize in this service.
What are GLP-1RAs (Weight loss medications)?
GLP-1RAs stand for glucagon-like peptide-1 receptor agonists. These medications mimic a hormone naturally found in the body and work by:
- Slowing how quickly food leaves your stomach
- Increasing appropriate insulin release
- Reducing unnecessary glucagon signaling
- Sending fullness signals to the brain
Initially, all GLP-1RAs were approved by the Food and Drug Administration (FDA) to manage type 2 diabetes. However, some of these medications have also been approved as weight-loss drugs. The most popular agents include semaglutide and tirzepatide. Compounded GLP-1RAs are often marketed for weight management since most insurance plans only cover the manufactured versions for type 2 diabetes.
What are compounded GLP-1RAs?
Compounded GLP-1RAs are made by outsourcing pharmacies that are not connected to the manufacturers of the brand-name products. These medications are designed to mimic the original products, but they are not FDA-approved generic medications.
Normally, it is illegal to copy a medication if the original product is still under patent. However, during an FDA-declared drug shortage, these medications can legally be compounded. Currently, semaglutide is in shortage, and tirzepatide was previously in shortage but is no longer. Despite this, tirzepatide is still being compounded because the FDA agreed not to prosecute compounding pharmacies while a lawsuit filed by one of these pharmacies is ongoing.
Risks associated with compounded GLP-1RAs
Advertising for compounded GLP-1RAs has increased, making them widely available. These products may provide a more affordable option for patients whose insurance doesn’t cover FDA-approved medications and could serve as an alternative during shortages. However, using these products comes with certain risks.
Adulterated and misbranded medications
Compounded GLP-1RAs have been the subject of numerous lawsuits. Manufacturers like Novo Nordisk (semaglutide) and Eli Lilly (tirzepatide) have sued compounding pharmacies for producing adulterated (contaminated or tainted) or misbranded products and for dispensing medications without proper prescriptions.
In the ongoing lawsuits the most commonly cited adulteration is compounding manufacturers dispensing contaminated medications or producing medications in unsanitary conditions. The most common instances of misbranding has been when compounded medications contain less active ingredient than advertised.
Risks of incorrect dosing
Reports of adverse events, including hospitalizations, have been linked to dosing errors with compounded GLP-1ra products. Across the country poison control centers saw a nearly 1,500 percent increase in calls in 2023 related to accidentally overdosing on injected weight-loss drugs.
The FDA dispersed an alert highlighting that these errors often stem from confusion with units of measurement (e.g., milliliters, milligrams, and units) and the variation in concentrations offered by different compounders. Unlike FDA-approved GLP-1ra, which are available in standard concentrations and prefilled pens, compounded versions may come in multiple-dose vials or prefilled syringes with varying strengths. This lack of standardization increases the risk of miscalculation or unintentionally drawing up an inappropriate dose. For example, patients unfamiliar with using syringes have accidentally administered 5–20 times the intended dose, and providers have miscalculated conversions from milligrams to units, leading to severe side effects and in some instances hospitalization.
The FDA estimates that 10 deaths and 100 hospitalizations may be linked to the use of compounded GLP-1RAs.
Lack of oversight and the FDA’s stance
The FDA has issued safety alerts when they become aware of specific compounding pharmacies operating illegally or notice safety issues, such as increased medication overdoses. However, their responses are often reactive, meaning action is usually taken only after a patient experiences a negative outcome. This delay is partly due to how the law defines the FDA’s authority over outsourcing compounding pharmacies.
The FDA states “as with all compounded drugs, drugs compounded by outsourcing facilities have not undergone FDA premarket review for safety, effectiveness, and quality, and lack a premarket inspection and finding of manufacturing quality that is part of the drug approval process. Because they are subject to a lower regulatory standard, compounded drugs should only be distributed to health care facilities or dispensed to patients to fulfill the needs of patients whose medical needs cannot be met by an FDA-approved drug.”
Talk to your health care provider about compounded weight loss medications or other options
Ultimately, deciding whether to use a compounded GLP-1RA is a personal choice that should involve a conversation between the patient and their prescriber. The key question to consider is: "Given my specific circumstances are the potential weight loss benefits of a compounded GLP-1RA worth the safety risks and side effects these medications pose?"
For more tips on living well, visit the Be Well blog.
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