Preprint counts 455 adverse event reports involving compounded tirzepatide

A preprint posted on medRxiv reports that the FDA's Adverse Event Reporting System (FAERS) contained at least 455 reports of adverse events involving compounded tirzepatide as of December 2, 2025, including 339 serious adverse events and 8 deaths ^[1]. The same paper describes a previously unidentified impurity found in compounded tirzepatide products that are combined with vitamin B12 ^[1].

The paper has not been peer reviewed ^[1]. Its authors work for Eli Lilly, the company that makes the FDA-approved tirzepatide drugs Mounjaro and Zepbound ^[1]. The preprint reports only counts from FAERS; it does not describe the individual reports, what the events were, who the patients were, or whether tirzepatide caused them ^[1]. Those details have not been disclosed.

The authors say they obtained ten samples of compounded tirzepatide combined with B12 analogs, including methylcobalamin and hydroxocobalamin, from compounding pharmacies, medical spas and telehealth networks across the United States ^[1]. Laboratory testing found a substance in every sample with a mass of about 6,138 Daltons — larger than tirzepatide alone, which the paper lists at 4,810.52 Daltons — consistent with a B12 molecule attached to tirzepatide ^[1]. The paper calls the result a tirzepatide–B12 adduct and says it made up as much as 10 percent of the total protein content in the samples tested ^[1].

Potency also varied. Some samples measured as low as 43 percent of the labeled tirzepatide value, according to the paper ^[1].

For comparison, the preprint says FDA expects makers of combination products to report any impurity present at 0.05 percent, identify any impurity present at 0.1 percent, and qualify any impurity present at 0.15 percent ^[1].

The paper states that the clinical effects of the impurity are unknown, and that there are no data on how it affects the safety or effectiveness of tirzepatide ^[1].

The preprint places these products in a wider context. After FDA determined in October and December 2024 that tirzepatide was no longer in shortage, many sellers shifted to fixed-dose combinations with vitamins and other additives, including B12 analogs ^[1]. The paper says the true scope of these practices is unknown because the products exist outside the federal regulatory framework for pharmaceuticals, and that sellers generally do not run premarket testing, register their establishments, follow current Good Manufacturing Practices, or report adverse events ^[1]. It cites data showing compounded drugs accounted for 45 percent of U.S. drug product recalls between 2012 and 2021 while making up less than 3 percent of prescriptions ^[1]. FDA has cautioned that compounded tirzepatide "can be risky for patients" ^[1].

Why it matters for patients

Compounded tirzepatide is not the same product as the FDA-approved versions. Mounjaro and Zepbound are manufactured under federal quality standards and tested before marketing, while the compounded products described in the preprint are not required to report, identify or qualify the impurities they contain ^[1]. The impurity the authors found was present at levels far above the thresholds FDA applies to approved combination products ^[1].

What that impurity means for a person taking a compounded product is not established. The preprint says its clinical effects are unknown and that no data exist on its impact on tirzepatide's safety or efficacy ^[1]. The FAERS numbers are counts of reports, and the preprint does not say how those reports were evaluated or whether the events were attributed to the drug ^[1]. A report in the database is not by itself a finding that a drug caused a problem, and the preprint does not make that claim.

One practical gap the paper highlights is information: it states that sellers of unapproved compounded tirzepatide products generally do not disclose their products or their volume, which leaves patients and clinicians with limited ability to know what is in a given vial ^[1].

What happens next

The paper has not been peer reviewed ^[1]. Whether it will undergo peer review, and whether FDA has taken or plans any action in response, has not been reported ^[1]. The adverse event figures it cites are as of December 2, 2025, and the preprint version was posted March 10, 2026 ^[1].