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

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.

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.

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.

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.