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.
26 products testedFollow-on injectable and oral semaglutide and liraglutide products from the global market, many showing quality differences from originator drugs
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
Who was studied
26 follow-on GLP-1 drug products compared against originator products (laboratory analysis, no human subjects)
What this study cannot 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.
How to read the evidence
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.
When this study was published
Published in 2024. Highly relevant given the ongoing global demand for GLP-1 drugs and the rapid growth of compounded and follow-on products.
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.
Questions still open
- 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?
Common questions
What's the difference between a follow-on product and a compounded product?
Does this mean compounded semaglutide is dangerous?
Read the original research
Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.
Pharmaceutical research, 41(10), 1991-2014
Citation
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