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Study breakdown

Most Compounded Semaglutide and Tirzepatide Use Goes Undocumented in Primary Care Records

evidence
The takeaway

Only 8.2% of GLP-1 medication users in a large US primary care database had documented compounded formulation use, far below the estimated 23% who actually obtain these drugs from compounders.

8.2% documented vs. ~23% estimated

The gap between documented compounded GLP-1 agonist use in primary care records and survey-based estimates suggests most compounded use occurs outside coordinated medical care.

What the researchers found

Among 153,044 patients with documented semaglutide and/or tirzepatide use in the American Family Cohort (a nationwide US primary care EHR database spanning 2021-2024), 8.2% had documented use of compounded formulations. This proportion increased over time as drug shortages drove more patients to compounding pharmacies.

Users of compounded formulations had notably different demographics: they were more likely to be female, non-Hispanic White, non-diabetic, and living in areas of lower socioeconomic deprivation. They also had longer mean therapy durations (10.0 months for compounded-only users vs. 7.8 months for brand-name-only users). The documented rate of 8.2% was substantially lower than the ~23% estimated by surveys, suggesting significant undocumented use outside coordinated primary care.

Why it matters

The rapid growth of compounded GLP-1 receptor agonists represents a major shift in how patients access peptide-based therapeutics. When patients use these medications without their primary care doctor's knowledge, it creates gaps in medication monitoring, drug interaction screening, and side effect management. This study quantifies that gap for the first time in a large dataset, highlighting a patient safety concern at the intersection of telehealth expansion, drug shortages, and consumer demand.

How the study worked

Retrospective cohort study using the American Family Cohort, a nationwide US database of electronic health records from primary care practices, covering January 1, 2021 to December 31, 2024. Brand-name prescriptions were identified from structured prescription data. Compounded formulation use was identified through clinical notes (unstructured text), reflecting what clinicians documented during visits.

What this study cannot tell us

Compounded use was identified from clinical notes, which may undercount actual documentation if notes were incomplete or used inconsistent terminology. The database represents primary care practices only and does not capture care delivered by telehealth companies or aesthetic clinics directly. The 23% survey estimate used as a comparison may have its own biases. The study could not assess clinical outcomes or adverse events associated with compounded formulations.

How to read the evidence

This is a large retrospective cohort study using real-world electronic health record data from over 153,000 patients nationwide. While observational and limited by documentation quality, the sample size and scope make it a strong pharmacoepidemiologic study.

When this study was published

Published in 2025 covering data through December 2024, this is highly current research capturing the peak of GLP-1 drug shortages and compounding pharmacy expansion. The regulatory landscape continues to evolve rapidly.

The bigger picture

This study captures a pivotal moment in the GLP-1 receptor agonist market. Semaglutide and tirzepatide have become among the most sought-after medications globally, and supply shortages drove an unprecedented expansion of compounding pharmacy access. The finding that most compounded use is invisible to primary care raises questions about medication safety oversight, the role of telehealth in bypassing traditional care coordination, and how the healthcare system should adapt to patient-driven demand for peptide therapeutics.

Questions still open

  • What clinical outcomes and adverse events are associated with compounded GLP-1 receptor agonist use compared to brand-name formulations?
  • How can primary care systems better capture and coordinate care for patients accessing medications through telehealth and compounding pharmacies?
  • Now that FDA shortage designations have changed, how will the pattern of compounded GLP-1 agonist use shift?

Common questions

Why are so many people using compounded versions of Ozempic and Mounjaro?
During 2022-2024, massive demand for semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) created drug shortages. Compounding pharmacies, telehealth companies, and aesthetic clinics stepped in to produce and sell compounded versions, often at lower prices and without requiring a traditional doctor visit. This made the drugs more accessible but often outside regular medical oversight.
Is it dangerous to use compounded GLP-1 medications without telling your doctor?
It can be. When doctors don't know about all the medications you're taking, they can't properly check for drug interactions, monitor for side effects like pancreatitis or thyroid issues, or adjust other treatments accordingly. Compounded formulations may also vary in quality and dosing accuracy compared to FDA-approved brand-name versions.

Read the original research

Documentation of Compounded GLP-1 Receptor Agonists in a Large Primary Care Dataset.

Pharmacoepidemiology and drug safety, 34(10), e70227

Citation

Hendrix, Nathaniel; Velásquez, Esther E; Pham, Harry; Bazemore, Andrew. (2025). Documentation of Compounded GLP-1 Receptor Agonists in a Large Primary Care Dataset.. Pharmacoepidemiology and drug safety, 34(10), e70227. https://doi.org/10.1002/pds.70227