Pediatric Use of Compounded GLP-1 Agents: Benefits, Risks, and Equity

Abstract

The American Academy of Pediatrics recently revised its guidelines on pediatric obesity treatment to recommend that primary care providers offer anti-obesity medications to patients based on age and body mass index. Anti-obesity medications like glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are efficacious in lowering body mass index (BMI) and improving metabolic health, including in children. However, although the landscape for medication production and insurance coverage is rapidly evolving, these medications can be difficult to access due to cost, lack of insurance coverage, and supply chain issues. Compounded versions of GLP-1 RAs offer the benefits of providing lower cost and higher availability alternatives to FDA-approved versions. But they include risks associated with less regulated medications. This paper identifies the risks and benefits of compounded GLP-1 RA use in the pediatric population, particularly considering structural inequities in obesity burden and treatment, and offers recommendations for pediatricians to ethically and equitable address compounded GLP-1 RA use with their patients and their families.

1. Introduction

Pediatric obesity continues to be a major health problem, with the prevalence of obesity in children at 18.6% in the US and 8.5% worldwide [1]. Youths with obesity most often become adults with obesity and, due to co-morbidities such as diabetes and cardiovascular disease, are at risk for a shortened lifespan [2]. Recognizing the scope of the problem, the American Academy of Pediatrics (AAP) revised its guidelines on pediatric obesity treatment to recommend that primary care providers offer anti-obesity medications (AOMs) to youths aged 12 and older with a body mass index (BMI) greater than or equal to the 95th percentile for age and sex [3].

AOMs like glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are efficacious in lowering BMI and improving metabolic parameters such as hemoglobin A1c, lipid profile, and liver transaminases in adults and youths [4,5,6]. While other AOMs are available, such as orlistat, phentermine, and topiramate, the demand for these alternatives is limited due to their side-effect profiles and reduced effectiveness compared to the GLP-1-RAs.

Following their Food and Drug Administration (FDA) approval, over 15 million Americans are now on GLP-1 RAs [7]. Studies show these medications to be effective for managing type 2 diabetes mellitus and obesity, with additional research indicating expanded benefits, such as to cardiovascular and renal health [8]. Specific to pediatrics, one real-world study on the use of GLP-1 RA liraglutide among children and adolescents with obesity showed that it was safe and effective for improving metabolic health and reducing adiposity [9]. Although the available body of research that supports significant benefits of GLP-1 RAs is growing, studies also suggest some notable side effects, and further study is needed across time and additional populations to address a wider range of safety and tolerability concerns [8].

With demand quickly exceeding supply, alongside the high cost of the medications and lack of uniform insurance coverage, access to GLP-1 RAs has been difficult and inequitable [10]. When critical shortages occur, such as with the introduction of GLP-1 RAs for obesity treatment, the FDA allows compounding of medications under Section 503 of the Federal Food, Drug, and Cosmetic Act [11]. As of 2025, the FDA announced that shortages of many anti-obesity medications were largely resolved, moving them off the shortage list and making it no longer permissible to compound them under Section 503 [12].

Given the demand for GLP-1 RAs, whether officially on the shortage list or not, patients continue to turn to online suppliers and compounding pharmacies, which often offer lower prices and a supply of GLP-1 RA products that mimic, but are not copies of, FDA-approved products [13]. In response, The Obesity Society, Obesity Action Coalition, and the Obesity Medicine Association issued a joint public statement recommending that patients avoid “compounded alternatives to GLP-1 medications,” as they may utilize formulations that have not been FDA-approved and may not be safe or effective [14]. Similarly, the FDA has raised safety concerns with compounded anti-obesity medications related to their composition, production, and storage [15]. Of note, as research identifies growing potential uses and benefits of GLP-1 RAs, these medications may be of increasing interest to patients given research supporting a variety of evidence-based off-label uses.

Structural inequities in access to GLP-1 RAs, including the fact that they are largely not covered by Medicaid, the primary health insurance provider for children in the US which provides low or no-cost insurance to individuals and families below income thresholds and with certain disabilities, and that obesity is more prevalent among populations more likely to be on Medicaid, such as racial and ethnic minority populations [16], raise significant questions regarding whether financial barriers are sufficient reasons for considering FDA-approved GLP-1 RAs as “unavailable” for pediatric use. Moreover, awareness that patients and their families may seek out compounded versions of GLP-1 RAs may lead to provider uncertainty about the ethical risks, benefits, and alternatives of recommending such medications to patients, even if they meet clinical criteria to receive this recommendation.

2. History of Compounding Pharmacies in the USA

The practice of pharmaceutical compounding predates modern medicine and is one of the earliest forms of individualized therapeutics. Early pharmacists were skilled practitioners who transformed botanical and mineral substances into therapeutic preparations tailored to individual patient needs. By the early twentieth century, most medications dispensed to patients were compounded locally, with estimates suggesting that between 60% and 75% of prescriptions in the 1930s required some degree of in-pharmacy compounding [17]. Regulatory oversight during this period was fragmented and largely state-based, reflecting the patient-specific nature of pharmaceutical practice at the time.

Following World War II, advances in industrial manufacturing and pharmaceutical science, such as the mass production of antibiotics, fundamentally reshaped drug development and distribution. Standardization, scalability, and centralized manufacturing became the dominant model. Pharmacists increasingly transitioned from compounders to dispensers of commercially manufactured products. However, compounding retained an important role for select clinical indications, such as pediatric dosing adjustments, allergen-free formulations, and alternative routes of administration for patients unable to use standard dosage forms.

Modern federal oversight of compounded medications developed in response to significant patient harm. In 2012, a nationwide outbreak of fungal meningitis linked to contaminated steroid injections produced by the New England Compounding Center resulted in dozens of deaths and hundreds of serious illnesses. This tragedy exposed substantial gaps in regulatory authority and oversight [18]. In response, Congress enacted the Drug Quality and Security Act (DQSA) in 2013, establishing the bifurcated regulatory framework that governs pharmaceutical compounding in the United States today [19].

Under Section 503A of the DQSA, traditional compounding pharmacies that prepare medications for individually identified patients with valid prescriptions are exempt from certain federal requirements applied to drug manufacturers. These requirements include current good manufacturing practice (CGMP) standards, premarket approval processes, and specific labeling requirements. These exemptions are intended to preserve access to patient-specific therapies but are coupled with important limitations, including prohibitions against compounding medications that are “essentially copies” of FDA-approved drugs unless a documented clinical difference exists to justify their use.

Section 503B of the DQSA created a distinct regulatory category for registered “outsourcing facilities,” which may compound medications at a larger scale and distribute them interstate without patient-specific prescriptions if they voluntarily register with the FDA. In exchange, these facilities are subjected to more rigorous federal oversight. This oversight includes compliance with CGMP standards, routine FDA inspections, and mandatory adverse-event reporting.

Adherence to CGMP standards mitigates certain manufacturing-related risks associated with compounded medications, such as environmental contamination, batch-to-batch variability, inadequate sterility assurance, and insufficient quality documentation. However, CGMP compliance does not address all sources of risk inherent to compounded products. Persistent risks include the use of unapproved ingredients, the absence of clinical trial data, and dosing complexities associated with non-standard delivery formats. These limitations are particularly salient in the context of compounded GLP-1 RAs.

Although FDA-registered 503B outsourcing facilities operating under current CGMP standards mitigate certain manufacturing-related risks—particularly those related to sterility, documentation, and quality control—compounded products remain unapproved drugs and do not undergo FDA premarket review for safety, efficacy, or bioequivalence [20,21]. Accordingly, 503B registration represents a risk mitigation framework rather than risk elimination, consistent with the statutory structure governing drug compounding during periods of drug shortage [20,22].

The differential regulatory oversight applied to compounded products reflects a statutory framework established by Congress through the Compounding Quality Act to balance timely access to medications with patient safety protections during periods of drug shortage, rather than a deficiency in regulatory oversight. The creation of distinct pathways under Sections 503A and 503B represents an intentional policy design accommodating varying clinical contexts and production scales, with corresponding differences in oversight.

3. Compounding Patented Drugs and GLP-1 Agent Access

The law provides a notable exception to its prohibition on the “essentially copies” restriction when an FDA-approved drug appears on the official drug shortage list [19]. This exception impacted GLP-1 RAs beginning in 2022, when unprecedented demand—driven largely by their effectiveness for weight management—outstripped manufacturing capacity and the FDA designated them as shortage medications [23], expanding GLP-1 RA availability, often at significantly lower costs than branded products.

The widespread compounding of GLP-1 RA during shortages has revealed substantial safety concerns illustrating clinical risks of compounded medications. Documented problems include dosing errors arising from multi-dose vial dispensing rather than the calibrated, prefilled pens used with approved products, sometimes resulting in hospitalization for overdose [24]; quality and sterility issues with preparations exempt from CGMP requirements; and the use of alternative active pharmaceutical ingredients with unknown safety and efficacy profiles [15]. The FDA has identified particularly troubling practices among some compounders, including the use of unapproved salt forms of semaglutide (sodium or acetate variants) rather than the base form used in FDA-approved products. These alternative active pharmaceutical ingredients have unknown safety and efficacy profiles [15]. This is in addition to quality and sterility issues when compounders are exempt from and not voluntarily participating in CGMP standards.

By early 2025 following increased GLP-1 RA production capacity, the FDA determined that the shortages had resolved, rescinding their authorization of compounding [12] unless a documented “significant difference” exists between a compounded preparation and the FDA-approved medication. The FDA has explicitly stated that lower cost does not constitute such a significant difference, although there now exists a market for consumer interest in lower cost alternatives, which is driving ongoing compounding. Ongoing compounding access to GLP-1 RAs, including for pediatric populations, would require formulations with a “significant difference” to meet legal requirements for compounded production. This introduces additional risks to patients if formulations depart from those with FDA-approved safety profiles. To avoid introducing avoidable harm, AAP guidance on harm reduction encourages standardization of compounded formulations to minimize risks to patients [25].

The termination of shortage designations also identified benefits of compounded GLP-1 RAs for patient access to treatment that became apparent when those access benefits concluded. Name-brand GLP-1 RA products carry substantial costs—often exceeding $1000 monthly—and remain unaffordable for many patients, including many patients on Medicaid, ACA marketplace, and employer-provided insurance plans that do not cover GLP-1 RAs for weight loss. Compounded versions can cost as little as around $100 per month [26]. Currently most states in the US do not cover GLP-1 RAs under their Medicaid programs when used to treat obesity in adults. A federal agreement with some pharmaceutical companies is set to take effect in 2026 to lower costs for Medicare patients of certain GLP-1 RAs, including those FDA-approved to treat obesity [27]. However, federal protections on Medicaid coverage for children through the Early and Periodic Screening and Diagnostic Treatment (EPSDT) may create opportunities for enhanced coverage of GLP-1 RAs for children. The EPSDT benefit requires states to cover “medically necessary” treatments allowable under Federal Medicaid, even if not covered by a state’s program, for Medicaid enrollees under 21 years old, with medical necessity being determined on a “case-by-case basis” [28].

Ethical tensions arise between safety assurance and treatment accessibility when compounding pharmacies offer GLP-1 RAs at considerably lower cost [29] but with other risks that patients may not appreciate or be aware of and that are difficult to evaluate given uncertainty about compounded product formulas and production conditions. Research has identified numerous online compounding operations that fail to disclose (or mislead about) their products being compounded or unapproved, omit risk information, and exaggerate benefits amidst regulatory ambiguity regarding whether standard pharmaceutical advertising restrictions apply [30,31]. While medicine respects and promotes adult patient autonomy to make decisions they believe to be in their best interest after evaluating the risks and benefits, inadequate information disclosure compromises patient autonomy by failing to provide them with information to make a choice tailored to their goals, values, and tolerance for risk. In pediatrics, parents have broad authority to make decisions they believe to be in the best interest of their children and their families. Again, access to adequate information is essential to acting within this parental authority.

For both adult patients considering AOM and parents or guardians of pediatric patients with obesity, cost may be a tangible risk they are weighing against anticipated benefits of treatment. On the one hand, lack of affordable FDA-approved options constrains patient autonomy and parental authority to choose desired treatments if they are unaffordable, while compounded options may enhance autonomy and authority by expanding the range of available options from which to choose. On the other hand, these cost-related risk–benefit considerations reveal an injustice that these are tradeoffs that only those lacking payors willing to cover GLP-1 RAs for obesity, or those unable to pay out of pocket, must consider.

4. Pediatric GLP-1 RA Compounding and Ethical Implications

Pediatricians may already have ethical concerns about implementing AAP guidelines for obesity treatment for their patients, especially in the context of limited resources. While the guidelines recommend intensive behavioral and lifestyle interventions (BLIs), including exercise and nutrition, these may not be accessible to patients due to geography, time, or financial resource limitations. Structured programs may not be available in rural and underserved areas. Research shows BLIs involve substantial costs to run and are burdensome to patients and providers [32]. Burdens to patients include the time associated with regularly attending programs and the access to, time taken to prepare, and affordability of nutritious foods.

The guidelines indicate that pediatricians may recommend anti-obesity medications (which include GLP-1 RAs and other AOMs) to some patients as young as 8 years old, meaning medication recommendations are permissible but not required, but they should recommend them to patients ages 12 and over with a BMI at or above the 95th percentile [3], meaning that recommending medications is strongly encouraged as the best care for patients meeting these criteria. The strength of the recommendation can also impact insurers’ willingness to cover medications, with stronger recommendations more likely to meet thresholds for medical necessity.

For patients for whom medication may be recommended, pediatricians might be inclined to offer medications, especially when barriers persist to other interventions. A 2025 viewpoint essay by Sanaka et al. considers how standard biomedical principles of autonomy, beneficence, nonmaleficence, and justice apply to weight loss medications for pediatric patients [33]. While they mention a recommendation to “educate about potential risks of compounded medications and non-FDA-approved therapies” to address the principle of nonmaleficence, they do not offer any discussion of this recommendation. We agree with Sanaka et al. that such education is essential to ethical use of anti-obesity medication in pediatrics, for reasons beyond nonmaleficence.

Patients may face access barriers to medications if they are not covered by insurance, and the possibility of patients turning to compounded GLP-1 RAs is an important risk for pediatricians to weigh when deciding whether to even introduce discussions of potential benefits from GLP-1 RAs with patients and their families. Learning about insurance coverage of GLP-1 RAs by the predominant insurers in a pediatrician’s patient population, including state Medicaid coverage for children, and about the potential to submit for consideration of medical necessity under the EPSDT benefit will also enable pediatricians to provide patients with cost information as part of shared decision-making and to advocate to payors on behalf of patients when appropriate.

Moreover, even if pediatricians do not introduce discussions about anti-obesity medications into their patient encounters, patients and families may be interested in them given their widespread attention in popular media and direct-to-consumer advertising of these products. Misleading or inaccurate information in public discourse or even marketed directly to consumers complicates informed decision-making by patients and their parents, including for compounded GLP-1 RAs. We recommend that pediatricians engaging in conversations with patients and families about overweight and obesity ask open-ended questions about what patients and families have heard about or are curious about regarding weight loss treatment. This may include asking directly what patients or families know about anti-obesity medications, even if the pediatrician is not currently recommending them for the patient, to assess possible opportunities to address misinformation or risks of alternative treatment options.

Pediatricians have an opportunity to counsel patients about the risks of compounded formulations to promote nonmaleficence. However, the specific risks of a particular compounded product may be difficult to identify. For example, compounded GLP-1 products supplied during and after drug shortages exist along a regulatory spectrum, ranging from FDA-registered 503B outsourcing facilities operating under current good manufacturing practice (CGMP) standards and 503A patient-specific compounding pharmacies to nontransparent online distribution channels. As a result, the degree of regulatory oversight and associated risk varies substantially across compounded products, rather than reflecting a uniform risk profile.

However, pediatricians also need to be mindful of the potential perceived benefits of compounded GLP-1 RAs to patients and their families, particularly against the backdrop of disparate burdens of pediatric obesity and inequitable access to evidence-based treatment, reflecting beneficence and justice principles. For patients who lack insurance coverage for GLP-1 RAs for obesity or who lack access to recommended behavioral and lifestyle therapies, they may view compounded GLP-1 RAs as enabling beneficial treatment and countering injustices in healthcare access and coverage. Thus, engaging in direct conversations about compounded GLP-1 RAs also promotes patient autonomy and parental authority to make decisions motivated by an all-things-considered approach to best interest and equitable care.

5. Conclusions

The temporary expansion of compounded GLP-1 RAs during shortages showed that compounding expanded treatment access yet introduced safety and regulatory concerns. With restrictions on compounded GLP-1 RAs again in effect, there is a tension between ensuring medication safety and enabling affordable treatment access. Available compounded alternatives to GLP-1 RAs will likely have even less oversight and higher risk profiles than those authorized during the FDA-declared shortage period. Pediatricians need to weigh the strength of a recommendation for medication against the possibility that patients seek out less-regulated lower cost alternatives. However, they also need to be aware that their patients may already be considering alternative weight loss medications including those available through telehealth prescribers.

Informed consent and shared decision-making require pediatricians to counsel patients about the risks and benefits of treatment options and their alternatives and document these discussions and resulting decisions. Pediatricians must decide whether to proactively or only reactively discuss compounded GLP-1 RAs with patients and their families, balancing the promotion of evidence-based practice with the realities of cost and access and a harm-reduction approach. Our recommendation is to be prepared to discuss these alternatives with patients reactively and to decide whether to proactively address compounded GLP-1 RAs based on an open-ended discussion with the patient and family about their weight loss concerns, goals, knowledge, and interests. We also recommend that subspecialists and professional societies focused on pediatric obesity provide standardized tools to educate pediatricians on how to have these conversations with their patients and families and to create decision aids to use in shared decision-making conversations.

Currently, compounded GLP-1 RAs for pediatric use lack pediatric safety and efficacy data, may differ in active ingredients, and carry a higher risk of dosing variability. Accordingly, they may only be considered as a potentially clinically and ethically supportable alternative treatment if efforts to obtain FDA-approved therapies are exhausted and the anticipated benefits of medication significantly outweigh potential risks due to necessity for treatment. Given that many serious harms of pediatric obesity are not immediate risks but rather contribute to increased risks for harms in adulthood and there are other available on-label AOMs that may be available to pediatric patients at lower costs or covered by insurance, it is unlikely that recommending compounded GLP-1 RAs will be ethically justifiable based narrowly on a clinical risk/benefit assessment according to currently available evidence. However, as we have discussed, there are considerations related to equity and justice, as well as patient autonomy and parental authority, that interface with this narrow clinical evaluation of benefit and harm.

If a family chooses a compounded product, maintaining the patient in one’s practice may reduce harm and promote a patient’s wellbeing by allowing continuous monitoring and timely counseling. Given the uncertain risk profiles of compounded GLP-1 RAs and the potential for benefit for some patients, there is substantial ambiguity as to if, and under what conditions, a parent choosing compounded GLP-1 RAs for their child would constitute medical child abuse. More tailored guidance regarding acceptable harm reduction versus reportable harm is necessary to support pediatricians and primary care providers in busy practices without appropriate expertise to make such determinations.

Ultimately, ethical dilemmas regarding compounded GLP-1 RA counseling and harm reduction highlight a broader problem: inequitable access to proven treatments. Narrowing that gap requires coordinated advocacy that reaches beyond the clinic to insurers, manufacturers, and policymakers.