Semaglutide is a medication belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists. It mimics a natural hormone that helps regulate blood sugar, slows stomach emptying, and signals fullness to the brain. Semaglutide is widely prescribed for managing type 2 diabetes and, at a higher dose, for chronic weight management. Compounded semaglutide is an alternative preparation created by a licensed pharmacy. This custom-made version is an adaptation of the commercially available drug and is not identical to the product manufactured by the pharmaceutical company.
Defining Pharmaceutical Compounding
Pharmaceutical compounding is the practice of combining, mixing, or altering ingredients to create a medication tailored to an individual patient’s needs. This practice is typically performed by a licensed pharmacist or physician in a state-regulated facility. Historically, compounding met patient-specific needs, such as removing an inactive ingredient that causes an allergic reaction or creating a liquid form for those who cannot swallow a tablet.
The law recognizes two main types of compounding pharmacies: 503A and 503B facilities. A 503A pharmacy compounds medications based on an individual prescription and operates under state board of pharmacy regulations. In contrast, a 503B outsourcing facility can compound larger batches without individual prescriptions, often supplying hospitals and clinics. These 503B facilities must adhere to higher quality standards, called Current Good Manufacturing Practice (CGMP), which are the same standards required of large pharmaceutical manufacturers.
Compounding is also permitted to address drug shortages, which significantly impacted semaglutide availability. When a commercially manufactured drug is listed on the Food and Drug Administration (FDA) drug shortage list, compounding pharmacies can legally produce a copy. This exception ensures continuity of supply for patients during periods of national unavailability. The ability to compound semaglutide legally is directly tied to the official status of the drug shortage.
The Chemical Difference in Compounded Ingredients
The FDA-approved versions of semaglutide, sold under brand names like Ozempic and Wegovy, contain the active pharmaceutical ingredient (API) in its base form. This base molecule underwent rigorous testing for safety, effectiveness, and quality before receiving approval. When a drug is compounded, the active ingredient must typically be the exact same API used in the approved product.
Many compounded semaglutide products, however, use a chemically modified version of the active ingredient, such as semaglutide sodium or semaglutide acetate. These are salt forms of the semaglutide molecule, created by complexing the peptide with sodium or acetate ions. Salt forms are often used because they can improve the API’s stability or solubility in water, making it easier to formulate into an injectable solution.
Despite the slight chemical difference, the salt forms are not the same ingredient the FDA approved. The use of semaglutide sodium or semaglutide acetate means the compounded product is chemically distinct from the FDA-approved base molecule. This distinction is significant because the salt forms have not been evaluated by the FDA for safety, efficacy, or quality, nor has their bioequivalence to the approved base product been established.
Regulatory Oversight and Legal Status
Compounded semaglutide products are not approved by the FDA; they have not been reviewed for safety, effectiveness, or quality assurance. Federal law permits compounding only under specific conditions, primarily when the FDA-approved drug is on the national drug shortage list. Once the shortage is resolved, compounding pharmacies must cease producing copies of the commercially available product.
The FDA has issued explicit warnings concerning the use of semaglutide salts, such as semaglutide sodium and semaglutide acetate, in compounded preparations. The agency is not aware of any legal basis for using these salt forms in compounding, as they are different active ingredients than the approved semaglutide base. Compounded products using these salt forms are not covered by the FDA’s New Drug Applications and are considered unapproved new drugs.
The regulatory environment highlights safety concerns regarding the quality of compounded versions. The FDA has received reports of adverse events related to compounded semaglutide, including issues with inconsistent potency and contamination. Dosing errors have also been reported, sometimes resulting from miscalculating the dosage of the concentrated compounded solution.
The lack of strict oversight on compounded drugs limits the ability to track problems; unlike manufacturers, most state-licensed compounding pharmacies are not federally required to report adverse events. Since the FDA considers the semaglutide shortage resolved, the agency has set deadlines for compounding pharmacies to stop production. Continued use of compounded semaglutide carries increased risks of unknown quality, purity, and effectiveness, especially after the salt forms have been explicitly warned against.