Experts debate how to balance patient safety and affordable access to weight-loss medications.
Apothecary Pharma recalled 22 vials of compounded tirzepatide injections nationwide because of concerns about sterility, USA TODAY reported on October 19. The recall followed a Food and Drug Administration (FDA) warning letter identifying substantial deficiencies in the pharmacy’s sterile-drug production practices. This incident reflects broader concerns about the safety of compounded glucagon-like peptide-1 receptor agonists (GLP-1s), medications used to treat diabetes and obesity.
Compounding pharmacies customize medications to meet individual patients’ needs, such as by adjusting dosages or removing allergens. Unlike FDA-approved drugs, however, compounded versions do not undergo the same premarket review for safety, effectiveness, and quality. When demand for GLP-1s outpaced supply in 2022, shortage designations allowed compounders to fill resulting gaps. FDA declared the tirzepatide shortage resolved in December 2024 and the semaglutide shortage resolved in February 2025, ending the temporary basis for mass-producing essentially identical copies.
Yet compounded GLP-1s remain on the market, in part because brand-name treatments can cost over $1,000 a month without insurance coverage. Proponents argue that individualized formulations and lower prices preserve access for patients whose needs existing approved products cannot meet. Affordability, however, does not establish that an unapproved product is equivalent to its FDA-reviewed counterpart. Researchers in a 2026 study identified a previously unreported impurity in sampled compounded tirzepatide-vitamin B12 products. An adverse-event analysis found higher reporting odds for contamination and manufacturing problems involving compounded products. These reports reinforce safety concerns about compounded GLP-1 products that bypass rigorous quality review.
Federal law sets the baseline for what may be compounded and limits compounding essentially identical copies when approved drugs are commercially available, subject to narrow exceptions. Sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act establish different pathways for compounding drugs, but neither pathway authorizes routine mass production of essentially identical copies when statutory conditions are unmet.
States cannot loosen this federal eligibility baseline, but they can impose additional sourcing and quality requirements. The division of oversight between FDA and state pharmacy boards, telehealth marketing, and disputes over whether particular formulations satisfy federal requirements complicate enforcement. State pharmacy boards oversee many pharmacies day to day, and FDA oversees registered outsourcing facilities and enforces federal requirements. Despite FDA’s warnings to sellers about misleading marketing, sellers can exploit uncertainty about the boundaries of legitimate customization to continue reaching consumers. For example, some companies have marketed combination products with superficial alterations such as added vitamin B12 as personalized alternatives. Such changes do not by themselves establish a legitimate medical need.
Commentators propose stronger enforcement, clearer standards for patient-specific compounding, and improved access to affordable approved treatments to address these concerns. They disagree about how regulators should distinguish legitimate customization from mass production that circumvents compounding restrictions.
In this week’s Saturday Seminar, experts examine how regulators can balance patient safety and affordable access to compounded GLP-1 medications after drug shortages.
- The use of compounded GLP-1 products has been associated with adverse events and dosing errors, according to Washington State University College of Pharmacy and Pharmaceutical Sciences professor Joshua J. Neumiller and several coauthors in their article in Diabetes Care. Neumiller and his coauthors explain that compounding expanded amid shortages but raises concerns about product quality, safety, and effectiveness because compounded products do not undergo FDA review for these factors. They also highlight risks from variable concentrations, dosing errors, and semaglutide salt forms that differ from the approved ingredient. They recommend switching to another FDA-approved medication when a compounded product is unavailable and urge regulatory authorities to prioritize patient safety and enforcement of compounding standards.
- Plaintiffs in growing GLP-1-related mass tort litigation in the United States are unlikely to succeed on claims that drugmakers failed to warn patients, given the challenge of proving that inadequate warnings caused their injuries, argues University of Missouri-Kansas City School of Law student Angelina Ferrara in her UMKC Law Review article. Beyond the litigation, Ferrara identifies gaps in the system for protecting patients, including insufficient attention to long-term drug effects, inadequate labeling, and limited oversight of prescription-drug promotions by telehealth companies and social media influencers. She argues that preventing future harm requires a more coordinated approach, with manufacturers conducting more safety research, physicians better communicating risks, and the FDA strengthening its regulatory oversight.
- The advertising and sales of compounded GLP-1 products may pose risks for consumers, write University of Utah professor Joseph Mattingly II and Boston University professor Rena M. Conti in an article in JAMA Health Forum. Mattingly and Conti contend that compounded GLP-1s exist in a regulatory gray zone, allowing producers to market to consumers while omitting potential risks and adverse effects. These marketing practices, according to Mattingly and Conti, contrast with those of prescription drugs, the advertising of which FDA regulates. Mattingly and Conti recommend requiring advertisements of compounded drugs to meet the same standards as FDA-approved prescription drugs and creating a task force independent of the FDA to determine which drugs belong on the drug shortage list.
- In an article in Expert Opinion on Drug Safety, Brad Jordan of Eli Lilly and Company and several coauthors discuss potential safety issues in compounded tirzepatide-vitamin B12 products arising from a widespread impurity they identified. The Jordan team tested compounded tirzepatide products with vitamin B12, an additive not present in FDA-approved tirzepatide products, and identified a tirzepatide-B12 adduct, an impurity formed by B12 bonding to tirzepatide. The Jordan team found a wide range of potencies in the samples. These results, according to Jordan and his coauthors, reflect broader safety issues with compounded products, such as insufficient quality control and less stringent testing. Jordan and his coauthors recommend requiring compounded drug vendors to conduct rigorous product testing before marketing their drugs.
- In a Missouri Medicine article, Apollo Care director of quality assurance Jared Dudding argues that compounded GLP-1 agonists ensure access to affordable alternatives to brand-name drugs such as Wegovy and Ozempic. Dudding acknowledges that compounded GLP-1s present safety concerns, but he cautions that brand-name formulations also carry risks of adverse side effects. To address concerns about product quality and safety, Dudding notes that FDA-registered outsourcing facilities must meet manufacturing and quality control standards that can make them a safer source of compounded drugs than less regulated sources. Dudding urges policymakers to balance patient safety and affordable access and suggests solutions such as increased insurance coverage for GLP-1 medications or expanded payment assistance programs for low-income patients.
- In an article in the Journal of the Academy of Public Health, Center for Medicine in the Public Interest president Peter Pitts argues that compounded GLP-1 drugs pose public health risks. Pitts explains that compounded drugs should not replace approved medicine outside of declared shortages, subject to limited exceptions, and cautions that compounded drugs do not go through the stringent FDA approval process. Pitts warns that GLP-1 compounders evade FDA regulations, for instance by insisting that their drugs are “personalized.” Pitts also expresses concern that compounders rely on unregulated foreign suppliers of pharmaceutical ingredients. Pitts advocates requiring large compounders to register as drug manufacturers, restricting illicit imports of pharmaceutical ingredients, and increasing enforcement resources at FDA.
