Lab Tests Find Quality Problems in Generic and Compounded Semaglutide and Liraglutide Products
Testing of 26 follow-on semaglutide and liraglutide products found new impurities, lower-than-labeled drug amounts, potential immune triggers, and stability problems compared to brand-name versions.
Quick Facts
What This Study Found
Extensive laboratory testing of 26 follow-on (generic/compounded) GLP-1 products — 16 injectable semaglutide, 8 oral semaglutide, and 2 injectable liraglutide — revealed significant quality concerns compared to brand-name originator products.
Key problems found: follow-on injectable semaglutide products contained new impurities including high molecular weight proteins, trace metals, anions, counterions, and residual solvents. Several oral semaglutide follow-ons had markedly less semaglutide than their labels claimed and showed different drug release profiles that could reduce how much drug actually gets absorbed. Some follow-on products contained neoepitopes — protein fragments not found in originators — that could trigger unwanted immune reactions. Liraglutide follow-ons showed increased tendency to form fibrils (protein aggregates), indicating reduced physical stability.
Key Numbers
26 follow-on products tested · 16 injectable semaglutide · 8 oral semaglutide · 2 injectable liraglutide · New impurities found including HMW proteins, trace metals, residual solvents · Oral products had less semaglutide than label claim · Neoepitopes indicating immunogenicity risk
How They Did This
Researchers compared commercially available follow-on GLP-1 products against originator products using multiple analytical techniques: various chromatography methods with UV and mass spectrometry detection, inductively coupled plasma optical emission spectroscopy and mass spectrometry (for metals), nuclear magnetic resonance, dissolution testing, computational immunogenicity prediction (peptide/MHC II binding), and fibrillation assays for physical stability.
Why This Research Matters
With GLP-1 drugs in massive demand, follow-on and compounded versions are flooding the market worldwide. This study provides hard analytical data showing that many of these products are not equivalent to brand-name Ozempic, Wegovy, Rybelsus, or Saxenda. The differences aren't theoretical — less drug than labeled, new impurities, and potential immune-triggering proteins are concrete safety and efficacy concerns. This is especially relevant as patients and providers navigate supply shortages and cost pressures.
The Bigger Picture
The GLP-1 drug market is one of the fastest-growing in pharmaceutical history, and the gap between demand and supply has created a booming market for compounded and follow-on versions. This study provides the most comprehensive analytical comparison to date, and the results raise important questions for regulators, clinicians, and patients. As countries develop regulatory pathways for follow-on peptide drugs, studies like this highlight why peptide manufacturing quality matters — small differences in production can create products that look the same on the label but behave differently in the body.
What This Study Doesn't Tell Us
This study was conducted by Novo Nordisk, the manufacturer of originator semaglutide (Ozempic/Wegovy) and liraglutide (Saxenda/Victoza), creating a potential conflict of interest. The analysis was laboratory-based only — the actual clinical impact of the identified differences on patient outcomes is unknown. The specific follow-on products tested were not named. Not all follow-on products on the market were tested.
Questions This Raises
- ?Do the identified quality differences actually translate to reduced efficacy or increased side effects in patients?
- ?Should regulators require clinical bridging studies for follow-on peptide products, not just analytical comparisons?
- ?How should patients and clinicians evaluate the safety of compounded GLP-1 products given these findings?
Trust & Context
- Key Stat:
- 26 products tested Follow-on injectable and oral semaglutide and liraglutide products from the global market, many showing quality differences from originator drugs
- Evidence Grade:
- This is a rigorous laboratory analysis using multiple validated analytical methods. However, it's industry-sponsored (Novo Nordisk is the originator manufacturer) and does not include clinical outcomes data. The analytical findings are solid but their real-world significance requires further study.
- Study Age:
- Published in 2024. Highly relevant given the ongoing global demand for GLP-1 drugs and the rapid growth of compounded and follow-on products.
- Original Title:
- Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.
- Published In:
- Pharmaceutical research, 41(10), 1991-2014 (2024)
- Authors:
- Hach, Morten, Engelund, Dorthe Kot, Mysling, Simon, Mogensen, Jesper Emil, Schelde, Ole, Haselmann, Kim F, Lamberth, Kasper, Vilhelmsen, Thomas Kvistgaard, Malmstrøm, Joan, Højlys-Larsen, Kim Bonde, Rasmussen, Tina Secher, Borch-Jensen, Jonas, Mortensen, Rasmus Worm, Jensen, Thomas Marker Thams, Kesting, Julie Regitze, Catarig, Andrei-Mircea, Asgreen, Désirée J, Christensen, Leif, Staby, Arne
- Database ID:
- RPEP-08330
Evidence Hierarchy
Frequently Asked Questions
What's the difference between a follow-on product and a compounded product?
A follow-on product is a manufactured copy of a brand-name drug, often sold in countries with different regulatory standards. A compounded product is custom-mixed by a pharmacy, sometimes to address shortages. Both bypass the originator's manufacturing process, which this study shows can lead to quality differences including impurities and inconsistent drug amounts.
Does this mean compounded semaglutide is dangerous?
The study found analytical differences but didn't test clinical outcomes — so we don't know yet whether these differences cause harm in patients. However, finding less drug than labeled, new impurities, and potential immune triggers are concerning signals that warrant caution and further study.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-08330APA
Hach, Morten; Engelund, Dorthe Kot; Mysling, Simon; Mogensen, Jesper Emil; Schelde, Ole; Haselmann, Kim F; Lamberth, Kasper; Vilhelmsen, Thomas Kvistgaard; Malmstrøm, Joan; Højlys-Larsen, Kim Bonde; Rasmussen, Tina Secher; Borch-Jensen, Jonas; Mortensen, Rasmus Worm; Jensen, Thomas Marker Thams; Kesting, Julie Regitze; Catarig, Andrei-Mircea; Asgreen, Désirée J; Christensen, Leif; Staby, Arne. (2024). Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.. Pharmaceutical research, 41(10), 1991-2014. https://doi.org/10.1007/s11095-024-03771-6
MLA
Hach, Morten, et al. "Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.." Pharmaceutical research, 2024. https://doi.org/10.1007/s11095-024-03771-6
RethinkPeptides
RethinkPeptides Research Database. "Impact of Manufacturing Process and Compounding on Propertie..." RPEP-08330. Retrieved from https://rethinkpeptides.com/research/hach-2024-impact-of-manufacturing-process
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.