A study in JAMA gives the clearest prescription-level view of what is inside compounded GLP-1 products, documenting additive combinations that exist in no FDA-approved version of these drugs.
What Happened
Researchers led by T. Joseph Mattingly II, PharmD, PhD, of the University of Utah College of Pharmacy analyzed Nebraska's prescription drug monitoring program, the first state system in the US to capture all dispensed prescriptions, including compounded products. Between January 2018 and April 2026 they identified 13,964 compounded weight-loss prescriptions dispensed to 6,089 patients: tirzepatide 36.6%, semaglutide 40.1% and phentermine 23.3%. Of those prescriptions:
- 99.5% of those prescriptions (13,888) were private pay — cash, charge or credit card — rather than billed to Medicaid, Medicare or commercial insurance.
- Compounded GLP-1 dispensing rose from 4,116 prescriptions in 2024 to 5,485 in 2025, when semaglutide and tirzepatide accounted for 86.4% of the 6,344 compounded weight-loss prescriptions. None appeared before 2024.
- All 10,711 compounded GLP-1 prescriptions came from out-of-state pharmacies. Three pharmacies in Florida and Texas accounted for 69.8%, though 42.8% of prescriptions were written by Nebraska prescribers.
- Two-thirds of tirzepatide prescriptions (67.8%) contained at least one vitamin B12 analogue. Cyanocobalamin appeared in 63.1% of tirzepatide and 39.7% of semaglutide prescriptions.
- Cyanocobalamin in tirzepatide fell from 85% to 54.4% between 2024 and 2025, while levocarnitine climbed from 0.4% to 16.0% — a shift the authors tie to the December 2024 shortage resolution and reformulation for clinical distinctness.
"These combination products undergo no premarket testing and carry no adverse event reporting requirements, so we cannot characterize the composition, stability, or clinical consequences of what patients are receiving," Mattingly said.
Who Is Affected
- Patients paying cash, whose treatments sit outside claims-based surveillance entirely.
- Prescribers, mostly nurse practitioners and physician assistants, writing for products they cannot verify.
- Pharmacovigilance systems and testing labs, which lack a field for compounded products and must instead test formulations that shift by pharmacy and by year.
Timeline
- January 2018 – April 2026 — study window for Nebraska compounded weight-loss prescriptions.
- December 2024 — the FDA resolves the tirzepatide shortage; B12 coformulation then declines as levocarnitine rises.
- 2025 — compounded GLP-1s reach 86.4% of compounded weight-loss prescriptions in the state.
- October 2026 — the study publishes in JAMA.
What This Means for Researchers
Two questions follow. First, whether coformulated additives alter stability or potency: an earlier paper identified a tirzepatide-B12 adduct impurity, and no comparable characterization exists for the other combinations dispensed. Second, whether the market can be monitored at all — near-universal cash payment and out-of-state dispensing mean claims data will never see it.
The authors call for pharmacovigilance infrastructure that tracks compounded products distinctly from brands; the pattern mirrors reviews in Colorado, West Virginia and Oklahoma. Their advice: do not assume a patient reporting tirzepatide or semaglutide is receiving an FDA-approved product. Adverse events should go to FDA MedWatch, still voluntary and the only surveillance available.
How to Verify Your Peptides
Additive-heavy formulations make identity testing more important, not less:
Safe Alternatives
FDA-approved incretin therapies are made under one validated process, without compounded additives. See our references for semaglutide and tirzepatide, browse the peptide library, and compare vendor profiles that publish third-party testing.
Sources
- JAMA, prescription-level analysis of compounded GLP-1 and weight-loss dispensing in Nebraska (2026)
- University of Utah College of Pharmacy research
- Industry reports on the compounded GLP-1 market