Effects of Zinc Leachate on the Structure and Activity of Semaglutide
- 1Department of Chemistry and Biochemistry, University of North Carolina Wilmington, 1040 Walton Drive, Wilmington, NC, United States, 28403
Abstract
Semaglutide is among the most prescribed Glucagon-like peptide-1 agonists (GLP-1As) for treatment of type II diabetes and obesity in both oral (Rybelsus®, Wegovy®) and injectable (Ozempic®, Wegovy®) formulations. Injectable semaglutide is often manufactured in prefilled syringes, which facilitate convenient storage and independent dosage for patients. Recently, potential leaching of zinc from the elastomer of the inner needle shield has been evaluated for pharmaceutical antibody formulations. The leached zinc ion may impose a risk of drug aggregation, particle formation, and needle clogging. In the present study, we experimentally examined the effects of Zn2+ on structure and in vitro activity of semaglutide. Our findings indicated that addition of Zn2+ induced a rapid increase in semaglutide’s α-helicity, followed by a gradual decrease in ellipticity under thermal stress at 37 °C. The zinc-stressed semaglutide did not cause cytotoxicity or loss of in-vitro activity, potentially due to the reversibility of their structural changes upon dilution. Moreover, we observed a protective role of phosphate, the formulation buffer of Ozempic and Wegovy, against Zn2+-induced stress. This work provides new insights for evaluating and mitigating the potential risk of zinc leaching in the injectable formulations of GLP-1 therapeutics.
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BibTeX
@misc{doran2026effects,
title = {{Effects of Zinc Leachate on the Structure and Activity of Semaglutide}},
author = {Emilia K. Doran and Rickey Su and Ying Wang},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009850/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009850/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Effects of Zinc Leachate on the Structure and Activity of Semaglutide
AU - Emilia K. Doran
AU - Rickey Su
AU - Ying Wang
PY - 2026
DA - 2026/10/05
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009850/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009850/v1
AB - Semaglutide is among the most prescribed Glucagon-like peptide-1 agonists (GLP-1As) for treatment of type II diabetes and obesity in both oral (Rybelsus®, Wegovy®) and injectable (Ozempic®, Wegovy®) formulations. Injectable semaglutide is often manufactured in prefilled syringes, which facilitate convenient storage and independent dosage for patients. Recently, potential leaching of zinc from the elastomer of the inner needle shield has been evaluated for pharmaceutical antibody formulations. The leached zinc ion may impose a risk of drug aggregation, particle formation, and needle clogging. In the present study, we experimentally examined the effects of Zn2+ on structure and in vitro activity of semaglutide. Our findings indicated that addition of Zn2+ induced a rapid increase in semaglutide’s α-helicity, followed by a gradual decrease in ellipticity under thermal stress at 37 °C. The zinc-stressed semaglutide did not cause cytotoxicity or loss of in-vitro activity, potentially due to the reversibility of their structural changes upon dilution. Moreover, we observed a protective role of phosphate, the formulation buffer of Ozempic and Wegovy, against Zn2+-induced stress. This work provides new insights for evaluating and mitigating the potential risk of zinc leaching in the injectable formulations of GLP-1 therapeutics.
ER -