The popularity of glucagon-like peptide-1 (GLP-1) agonists for weight loss (tirzepatide [Zepbound], semaglutide [Wegovy], and liraglutide [Saxenda]) has outpaced the supply of the FDA-approved medications. Drug shortages of GLP-1 agonists have inflamed a market of compounded drugs to meet demand. However, reports have raised concerns about increased risks of dosing errors with compounded medications due to incorrect self-administration and/or miscalculated doses by healthcare providers, which have led to hospitalization in some cases. As of November 2024, the FDA has received 392 and 215 reports of adverse effects associated with compounded semaglutide and tirzepatide, respectively.
In addition to concerns associated with compounded medications, the storm of high drug costs, drug shortages, and high demand has contributed to the introduction of counterfeit GLP-1 agonists to the market. These counterfeit medications are dispensed by illegal online pharmacies without a prescription. A recent audit of semaglutide samples from three online pharmacies showed that the measured amount of semaglutide exceeded the expected dosage by 29-39 percent, with one sample being potentially contaminated (elevated endotoxin levels, but no viable organisms detected).
High demand for GLP-1 agonists is contributing to a shift in the healthcare paradigm, in which patients can access medications through online direct-to-consumer providers with pharmacy relationships. In these care models, patients connect with online providers who prescribe medications, which are then filled by partner pharmacies that specialize in compounding these drugs. For GLP-1 agonists, pharmacies have reported offering the compounded version at lower prices than commercially manufactured products. One digital health platform offering weight loss services (in addition to other services) reported outpacing Wall Street analyst predictions over the last year. Recently, a popular weight loss program announced that it will be offering compounded semaglutide to increase access to patients. Interestingly, at least one online platform has partnered with specific pharmaceutical companies to provide certain drugs at lower cost to patients.
Given the changing health care landscape, many people will obtain GLP-1 agonists from “nontraditional” healthcare settings; providers, notably primary care providers, can expect to see patients who have started GLP-1 agonist therapy via these means. This highlights the need for all clinicians to be advocates for patient safety and ensure patients are obtaining and using GLP-1 agonists safely.
Pearls for ensuring safe access to GLP-1 agonist therapy and use of compounded formulations
GLP-1 agonists are prescription only medications. Online websites advertising GLP-1 agonists without a prescription may be a no-delivery scam or provide products that are either contaminated or an incorrect dose. In the audit of semaglutide samples from online pharmacies, the investigators reported never receiving product from three pharmacies in a confirmed nondelivery scam operation. Patients should be advised to avoid obtaining GLP-1 agonist medication from sources that do not require a prescription.
Healthcare providers should advise patients not to obtain GLP-1 agonists that are labeled “for research purposes” or “not for human consumption” or from illegal online pharmacies. These products are sold illegally with unknown quality that may be harmful, may be counterfeit, or contain wrong ingredients or the incorrect amount of ingredients. Additionally, certain GLP-1 products should not be used in compounded products. For example, the FDA states that the salt forms semaglutide sodium and semaglutide acetate are different active ingredients than semaglutide, and therefore cannot be legally used in compounding. If a patient chooses to use an online pharmacy to obtain GLP-1 agonists, they should be advised to be vigilant and only purchase from state-licensed pharmacies.
GLP-1 agonists may be compounded if in short supply. However, if FDA-approved drugs are commercially available, drugs cannot be compounded. For example, the recent tirzepatide shortage resolved in October 2024, with the FDA reaffirming that compounding should cease once patient access has stabilized (i.e., following a grace period to allow transition to a commercially available formulation or another agent). Of note, compounded drugs are not subject to FDA approval, meaning the FDA does not review the product for efficacy, safety, or quality. The FDA has reported areas of concerns and is currently working with compounders to resolve these concerns. Patients should be aware of potential safety risks with compounded products.
Healthcare providers and compounding pharmacies must provide the appropriate syringe size and education on measuring the correct dose. Patients and providers should be aware of overdose signs and symptoms, which include nausea, vomiting, and hypoglycemia. If these symptoms occur, patients should be advised to seek medical attention.
Finally, in addition to advising patients on safe acquisition and use of GLP-1 agonists, all clinicians can be vigilant in providing optimal care related to obesity management. While online direct-to-consumer services have increased access and addressed barriers to obesity management, they also present challenges associated with treating obesity within a silo. All clinicians should work to provide management and monitoring of obesity-related comorbidities. Additionally, clinicians should check for drug interactions between weight loss drugs and other medications which may be overlooked if patients use separate pharmacies for weight loss drugs, reaffirm proper use and administration techniques, and ensure frequent follow-up to manage adverse effects to optimize patient safety.
