Many Americans received compounded semaglutide and tirzepatide when these drugs were in shortage, but there is little understanding of how and how often they were used, limiting our ability to ensure safety, coordination, and appropriate regulation. We analyzed retrospective cohort data from the American Family Cohort from January 2021 to December 2024. We identified patients with documented semaglutide or tirzepatide use, categorizing them by brand and/or compounded drug exposure. Brand prescriptions were extracted from structured data; compounded drug use was identified from clinical notes. Among 153,075 included patients (64.0% female, mean age 55.0 years), 8.3% used compounded formulations. Compounded drug users had longer therapy durations versus brand-only users. Documentation rates of compounded semaglutide and tirzepatide use in primary care appear lower than survey-reported usage, suggesting that many patients received these medications outside coordinated care. Improved data interoperability, regulatory oversight, and clinical guidance are needed.

The authors have declared no competing interest.

The study did not receive any funding.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of the American Academy of Family Physicians waived ethical approval for this work.

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