FAERS analysis counts hundreds of compounded tirzepatide adverse events

A preprint posted to medRxiv reports that as of December 2, 2025, the FDA's Adverse Event Reporting System (FAERS) contained at least 455 reports of adverse events involving compounded tirzepatide, including 339 serious adverse events and 8 deaths ^[1]. The figure appears in the background section of a paper whose main subject is a newly described chemical impurity found in compounded tirzepatide mixed with vitamin B12 ^[1].

Two things about the source matter up front. The paper has not been peer reviewed, and medRxiv states plainly that it "was not certified by peer review" ^[1]. All five listed authors work for Eli Lilly and Company, which makes the FDA-approved tirzepatide products Mounjaro and Zepbound ^[1]. Compounded tirzepatide competes with those products.

What the paper found in the vials

The researchers bought compounded tirzepatide-plus-B12 products from compounding pharmacies, medspas and telehealth networks across the United States and tested them using liquid chromatography-mass spectrometry and nuclear magnetic resonance ^[1]. Ten samples were analyzed ^[1].

Potency varied widely against a tirzepatide reference standard, with some samples measuring as low as 43% of the labeled amount ^[1]. Every sample tested also contained a previously unidentified impurity with a mass of roughly 6,138 daltons, compared with 4,810.52 daltons for tirzepatide alone ^[1]. The authors concluded the impurity is a tirzepatide-B12 adduct, meaning a B12 molecule chemically attached to the drug, and it made up as much as 10% of total polypeptide content in the samples ^[1].

For comparison, the paper notes that FDA manufacturing rules require reporting any impurity present at 0.05%, identifying any at 0.1%, and qualifying any at 0.15% ^[1]. The authors state there are currently no data on how this impurity affects the safety or effectiveness of tirzepatide ^[1]. They describe the clinical effects as unknown ^[1].

Context on the numbers

The paper cites a separate FAERS analysis concluding that compounded tirzepatide "may be associated with significantly higher odds of adverse events, safety concerns and product quality issues" than FDA-approved tirzepatide ^[1]. It also cites data that compounded drugs accounted for 45% of all US drug product recalls between 2012 and 2021 while making up less than 3% of prescriptions, with lack of assurance of sterility the leading recall reason ^[1].

FAERS counts have limits the preprint does not fully spell out. The paper itself notes that sellers of unapproved compounded tirzepatide generally do not report adverse events to FDA, which suggests the 455 figure may undercount ^[1]. At the same time, a FAERS report is a report, not a confirmed cause-and-effect finding; the preprint does not say the 8 deaths were verified as caused by compounded tirzepatide ^[1].

Why it matters for patients

Many people started on compounded tirzepatide during the shortage period. FDA determined in October and December 2024 that tirzepatide was no longer in shortage, and the paper says many sellers then shifted to fixed-dose combinations of tirzepatide with vitamins and additives, including B12 analogs such as methylcobalamin or hydroxocobalamin ^[1].

The practical takeaway from this analysis is about uncertainty. Compounded combination products are not evaluated in clinical studies that test each ingredient separately and together, are not held to the same purity standards, and are not required to identify or qualify impurities ^[1]. The authors say these products are marketed as comparable to FDA-approved tirzepatide "even though they undergo no evaluation of their potency or impurity profiles" ^[1]. A vial with 43% of labeled potency and one with full potency would not look different to a patient ^[1].

FDA has cautioned that use of compounded tirzepatide "can be risky for patients" ^[1].

What happens next

The FAERS snapshot is dated December 2, 2025 ^[1]. The preprint version cited here was posted March 10, 2026 and carries a CC-BY-NC-ND license ^[1]. Whether it clears peer review, and whether independent laboratories confirm the tirzepatide-B12 adduct in other products, is not yet known. The paper does not report any FDA enforcement action, recall or safety communication tied specifically to this impurity, and it does not say whether the impurity has any clinical effect at all ^[1].