Obesity, characterized by excessive fat accumulation, presents significant health risks and impacts overall quality of life. The increasing prevalence of obesity worldwide has led to a surge in demand for effective weight management strategies, including pharmacological interventions like glucagon-like peptide-1 (GLP-1) receptor agonists. These medications have revolutionized the management of type 2 diabetes and obesity by improving glycemic control and promoting weight loss. However, the high demand and occasional shortages of brand-name GLP-1 drugs have led to the rise of compounded versions, raising questions about their effectiveness, safety, and regulatory oversight.
The Rise of Compounding Pharmacies
Compounding pharmacies have gained prominence due to their ability to create customized medications tailored to individual patient needs. Any pharmacy that provides medications that are not commercially available and prepares them onsite to meet specific needs is a compounding pharmacy.
Reasons for Using Compounding Pharmacies
There are a few different reasons why someone may need a compounding pharmacy. One common reason is when a patient requires a specific dosage or formulation that is not available in commercially manufactured drugs. This may also be the case when a patient needs a different dose or route of administration or if a patient is allergic to a certain ingredient in an FDA-approved medication. Another time you may require a compounding pharmacy is when there are drug shortages.
Compounded GLP-1 Receptor Agonists
Compounded GLP-1 receptor agonists have emerged as substitutes for branded weight-loss products during times of high demand or limited availability. The FDA has issued multiple safety communications addressing significant concerns about the use of compounded GLP-1 receptor agonists, particularly semaglutide and tirzepatide, for weight management.
Understanding Compounded Medications
Compounded medications are medications that are prepared by compounding pharmacies to meet individual patients' needs that cannot be met by FDA-approved brand name or generic medications. Compounding is the process of combining, mixing, or altering ingredients of a drug in order to prepare a medication customized for a specific patient. This customization 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, and creating specific doses that are not commercially available.
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Types of Compounding Pharmacies
Compounding pharmacies (503A pharmacies) create and dispense customized medications for individual patients by combining, mixing, or altering ingredients, often when commercial products are unavailable or unsuitable due to allergies or specific patient needs. Outsourcing facilities (503B facilities) are specialized types of pharmacies that are authorized to compound sterile drugs in bulk for distribution to healthcare providers, often to address shortages or specific patient needs. Unlike 503A compounding pharmacies, which prepare medications based on individual prescriptions, 503B facilities can produce large quantities without individual prescriptions, making them crucial for widespread distribution. These facilities must adhere to stringent FDA requirements, including compliance with Current Good Manufacturing Practices, registration with the FDA, and regular inspections to ensure product quality and safety.
GLP-1 Receptor Agonists: How They Work
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.
Safety Concerns and Regulatory Oversight
Unlike the drugs you purchase at a local pharmacy, compounded drugs aren't FDA-approved. While compounded drugs are always supposed to contain FDA-approved ingredients, the formulations as prepared at compounding pharmacies aren't reviewed by the FDA for purity, safety, or effectiveness. As a result, there's a chance that you may not be getting the drug that you think you are. The FDA has identified some areas of concern for compounded GLP-1 drugs.
Lack of FDA Approval and Oversight
A compounded drug might be appropriate if a patient’s medical need cannot be met by an FDA-approved drug, or the FDA-approved drug is not commercially available. However, compounded drugs are not FDA approved. This means the agency does not review compounded drugs for safety, effectiveness or quality before they are marketed. The agency has identified some areas of concern for compounded GLP-1 drugs. FDA is working with its state regulatory partners and will continue to communicate with compounders regarding these concerns.
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Dosing Inconsistencies and Errors
Dosing can also be less reliable with compounded drugs. FDA-approved injectable semaglutide products, for example, are only available in pre-filled pens, so it's harder for health care providers or patients themselves to make mistakes. But compounding pharmacies may load the pens with medication themselves, or expect patients to do so. The FDA has received reports of health providers calculating an incorrect dose, or patients giving themselves an incorrect dose. This can lead to potentially serious side effects like nausea, vomiting, headache, or acute pancreatitis. The compounding pharmacy may not give patients adequate instruction. There are reports of patients mistakenly giving themselves 20 times the appropriate dose.
Compounded GLP-1s often come in vials or syringes instead of prefilled pens, requiring patients to measure doses manually. FDA received multiple reports of adverse events, some requiring hospitalization, that may be related to dosing errors associated with compounded injectable semaglutide products. These dosing errors resulted from patients measuring and self-administering incorrect doses of the drug, and in some cases, health care professionals miscalculating doses of the drug. Additionally, the agency has received adverse event reports that may be related to patients prescribed compounded semaglutide or tirzepatide products in doses beyond what is in the FDA-approved drug label. This could mean using more product in a single dose, taking doses more frequently or increasing the amount more quickly (titration schedule).
Risk of Contamination and Impurities
Since compounding pharmacies themselves aren't FDA-regulated, there's also a greater risk of drug contamination. That's what happened in 2012, when patients developed fungal meningitis after receiving contaminated spinal injections of a compounded product. Compounding pharmacies are not subject to the rigorous quality control, clinical testing, and manufacturing standards required for FDA-approved drugs. This increases the risk of contamination and impurities within the products, although this risk is expected to be reduced with batch testing at 503B outsourcing facilities.
Use of Unapproved Salt Forms
The agency is aware that some semaglutide products sold by compounders may be the salt forms. These salt forms, including semaglutide sodium and semaglutide acetate, are different active ingredients than are used in the approved drugs. The agency does not have information on whether these salts have the same chemical and pharmacologic properties as the active ingredient in the approved drug, and we are not aware of any lawful basis for their use in compounding.
Adverse Event Reporting
Adverse events for compounded products may be underreported because federal law does not require state-licensed pharmacies that are not outsourcing facilities to submit adverse events to the FDA. FDA has received reports of adverse events related to compounded versions of semaglutide and tirzepatide. However, federal law does not require state-licensed pharmacies that are not outsourcing facilities to submit adverse events to FDA so it is likely that adverse events from compounded versions of these drugs are underreported.
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Identifying Legitimate Compounding Pharmacies
It can be tricky to identify a legitimate compounding pharmacy. Your doctor may already use a compounding pharmacy with other patients and may be able to refer you to one they know is reliable.
Questions to Ask
- What training do your pharmacists have?
- What other accreditation does your pharmacy have?
- Make sure the supplying pharmacy is registered to do business in the state.
Red Flags
- Be wary of buying compounded drugs online, whether it's through an online pharmacy or a telehealth platform.
- Be wary of online sites with no medical oversight.
- Carefully check labels of compounded GLP-1 drugs for warning signs such as spelling errors or incorrect addresses and ensure your medicine is provided by a licensed pharmacy and prescribed by a licensed health care provider.
- If you receive a product with a licensed pharmacy name on the label that you think might be fraudulent, contact the pharmacy to ask if it is their product.
The End of Shortages and FDA Enforcement
The FDA determined that the shortages of semaglutide and tirzepatide injections are resolved-tirzepatide as of December 2024 and semaglutide as of February 2025. This announcement triggered deadlines for compounders to cease production. With the official end of the national GLP-1 shortage, compounding pharmacies and outsourcing facilities are restricted from producing and selling mass-market compounded versions of these drugs. The manufacturers of several key GLP-1 products have filed multiple lawsuits against compounding pharmacies and telehealth companies for selling unauthorized versions of GLP-1 products and for copyright infringement.
FDA Recommendations
Compounded drugs should only be used in patients whose medical needs cannot be met by an FDA-approved drug. Patients should obtain a prescription from their doctor and fill the prescription at a state-licensed pharmacy. Visit FDA’s BeSafeRx campaign for resources to safely buy prescription medicines online. Talk to your doctor if you have questions about your medicines.
Alternatives to Compounded GLP-1s
Patients may have coverage of the FDA-approved brand-name products through their insurance provider. With a growing list of approved indications for these drugs, such as sleep apnea or cardiovascular disease, coverage may be available even if GLP-1s are excluded for weight loss. For patients who lack coverage, two major manufacturers have created direct-to-consumer programs that offer a cash price significantly lower than the standard price of their products. Manufacturers may offer savings cards, copay assistance, or patient assistance programs for eligible patients. These can help reduce out-of-pocket costs for brand-name GLP-1 medications.
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