Compounded GLP-1s carry three risks the branded products control for: the wrong active ingredient, uncharacterized impurities and dosing errors. FDA counts hundreds of adverse-event reports with compounded semaglutide and tirzepatide. And immunogenicity is real even at pharmaceutical standards, which is why impurity limits matter.
Key points
- As of May 2026 the FDA counted 990 reports with compounded semaglutide and more than 730 with compounded tirzepatide [1].
- Compared with branded products, compounded GLP-1s were associated in FAERS with more hospitalization (ROR 2.35) and contamination (ROR 19.0) [2].
- In the weight-reduction trials, branded tirzepatide produced anti-drug antibodies in 64.5% of patients. Hypersensitivity was 6.2% with antibodies vs 3% without [6].
- In its guidance for synthetic generics of five peptides with recombinant reference products (liraglutide among them), the FDA considers a new impurity above 0.5% not acceptable [7].
US status (October 2026): Semaglutide and tirzepatide are FDA-approved and off the shortage list. A 503A pharmacy may compound them only for a named patient inside FDA’s essentially-a-copy limits, and 503B facilities have no bulk pathway. See the semaglutide and tirzepatide status pages.
FDA is counting the reports
The FDA keeps a page on unapproved GLP-1s. “As of May 31, 2026” it had 990 adverse-event reports with compounded semaglutide and more than 730 with compounded tirzepatide, and it notes these are likely underreported [1]. It also clarifies a technical point that affects many products: “These salt forms, including semaglutide sodium and semaglutide acetate, are different active ingredients” from the approved drug, and retatrutide and cagrilintide “cannot be used in compounding under federal law” [1].
For your formulary, that means the salt matters. A pharmacy that compounds from a salt form is not compounding the approved drug’s active ingredient. The compounded GLP-1 after the shortage guide covers the copy rules in detail.
Pharmacovigilance shows signals, not rates
A FAERS analysis (2018 to 2024) compared 707 reports for compounded GLP-1s with those for branded products, out of 81,078 GLP-1 reports. Compounded products were associated with more hospitalization (ROR 2.35), product contamination (ROR 19.0) and preparation errors (ROR 48.9) [2]. By contrast, administration and dosing errors were reported proportionally less often with compounded products (ROR 0.29 and 0.24) [2]. It is a disproportionality analysis: it shows signals, not causes or rates.
Case series describe serious dosing errors. One poison center reported three cases with compounded semaglutide, two of them 10-fold dosing errors, and one patient who dosed in milliliters and units rather than milligrams [3]. Another series described three unintentional semaglutide overdoses at treatment initiation, such as 2 mg instead of 0.1 mg or 2.4 mg instead of 0.25 mg, with nonspecific gastrointestinal symptoms and no hypoglycemia [4].
- 990: reports with compounded semaglutide (FDA, May 2026) [1]
- ROR 19: contamination, compounded vs branded (FAERS) [2]
- 64.5%: anti-drug antibodies with branded tirzepatide [6]
B12 blends introduced a new impurity
In 2026, authors from Eli Lilly, the maker of branded tirzepatide, described a previously unidentified, widespread impurity in mass-compounded tirzepatide/B12 products. It is the result of a chemical reaction between tirzepatide and certain vitamin B12 analogs, present at substantial levels. Its clinical effect is unknown [5]. Read the source with its authorship in mind, and read the finding with the same care.
Immunogenicity is the issue almost nobody mentions
Peptides are immunogenic even when made to pharmaceutical standards. According to the Zepbound label, 64.5% of patients (1,591 of 2,467) developed anti-drug antibodies. Of those, 40% cross-reacted with native GIP and 16.5% with native GLP-1. Hypersensitivity was 6.2% in patients with antibodies vs 3% without, and injection-site reactions 11.3% vs 1%. Neutralizing antibodies against activity at the GIP or GLP-1 receptors were uncommon (2.8% and 2.7%), and the label cautions that incidence depends on the assay used [6].
Impurities and aggregates can raise that risk. In its guidance for synthetic generics of glucagon, liraglutide, nesiritide, teriparatide and teduglutide, the FDA asks for new impurities between 0.10% and 0.5% to be identified, characterized and justified, including comparative immunogenicity testing, and states that a new impurity “> 0.5% is not acceptable” [7]. The same logic appears in its risk entry for TB-500: immunogenicity “due to the potential for aggregation as well as peptide-related impurities” [8].
The source belongs in the chart
Compounded products and those from outside the regulated chain do not undergo that evaluation of potency and impurities [5][7]. When a patient has an allergic reaction, a persistent nodule or loss of effect, record the product’s source and certificate of analysis in the clinical history [2][5][6].
For your sourcing decisions:
- Confirm the active ingredient is the base drug, not a salt form [1].
- Ask the pharmacy how it tests for impurities, and get the certificate of analysis for each lot. The 503A vs 503B sourcing guide explains what each pharmacy type is held to.
- Write doses in milligrams and the matching volume, and teach the patient on the actual syringe [3][4].
- Treat a combination product, such as a B12 blend, as its own preparation with its own evidence gap [5].
References
- U.S. Food and Drug Administration. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. Updated 1 October 2026. Link
- McCall KL, et al. Safety analysis of compounded GLP-1 receptor agonists: a pharmacovigilance study using FAERS. Expert Opin Drug Saf. 2026;25(3):581-588. PMID 40285721. Link
- Lambson JE, et al. Administration errors of compounded semaglutide reported to a poison control center – case series. J Am Pharm Assoc. 2023;63(5):1643-1645. PMID 37392810. Link
- Wiener BG, et al. Challenges with glucagon-like peptide-1 (GLP-1) agonist initiation: a case series of semaglutide overdose administration errors. Clin Toxicol. 2024;62(2):131-133. PMID 38470137. Link
- Jordan B, et al. A novel, widespread impurity in mass-compounded tirzepatide/B12 products. Expert Opin Drug Saf. 2026;25(5):837-845. PMID 42010938. Link
- Eli Lilly and Company. Zepbound (tirzepatide) US prescribing information, revised 08/2026. Link
- U.S. Food and Drug Administration, SBIA. ANDAs for certain highly purified synthetic peptide drug products that refer to listed drugs of rDNA origin (presentation slides). 2022. Link
- U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. Link
This is general information, not medical or legal advice. Rules vary by state and change. Confirm your own facts with counsel.