Semaglutide and Liraglutide Modulate Oxidative Stress and Wound Repair in Normal Human Skin Cells Exposed to an In Vitro Diabetic-like Environment

Semaglutide was more protective than liraglutide in human skin fibroblasts under a diabetes-like stress, improving cell survival and lowering oxidative damage while speeding wound closure. Both GLP-1 receptor agonists supported antioxidant and collagen responses, and semaglutide neared complete wound healing within 48 hours. Keratinocytes did not respond to either drug.

Journal article — In vitro cell culture study. Population: Normal human dermal fibroblasts (NHDFs) and keratinocytes (NHEKs) under diabetes-mimicking conditions. Follow-up: 48 h. Interventions: Semaglutide, 22.5 and 45 pg/mL; Liraglutide, 22.5 and 45 pg/mL.

In NHDFs, semaglutide at 22.5 and 45 pg/mL for 48 h significantly improved viability and proliferation and reduced ROS more effectively than liraglutide. Apoptosis markers shifted toward survival, with higher Bcl-2 and lower Bax and cleaved caspase-3, particularly with semaglutide. Semaglutide uniquely increased Pax-7 expression. Both agents increased antioxidants and collagen expression and accelerated wound closure, with semaglutide achieving near-complete healing within 48 h and more strongly suppressing AGEs/RAGE and inflammatory cytokines. Neither drug induced observable changes in NHEKs.

For researchers studying liraglutide, this paper provides a head-to-head cellular comparison with semaglutide in a diabetes-mimicking skin model, showing that liraglutide can still improve antioxidant, collagen, and wound-closure responses even where semaglutide appears stronger. It does not establish clinical efficacy, dosing, or safety for either drug in patients.

Key findings

• Semaglutide significantly improved viability and proliferation of human dermal fibroblasts under high glucose/hydrogen peroxide conditions and reduced ROS more effectively than liraglutide.
• Apoptosis decreased with both drugs, as shown by increased Bcl-2 and decreased Bax and cleaved caspase-3, particularly with semaglutide.
• Semaglutide uniquely activated Pax-7 expression in diabetic-like NHDFs.
• Both agents upregulated antioxidants, but semaglutide more effectively suppressed AGEs/RAGE and inflammatory cytokines.
• Both drugs increased collagen expression and accelerated wound closure; semaglutide achieved near-complete healing within 48 h.
• Neither drug induced observable changes in NHEKs.

Limitations

• In vitro design cannot capture the full systemic environment of diabetic wound healing.
• No animal or human in vivo confirmation is provided; the authors call for further in vivo investigation.
• Effects were observed in fibroblasts but not keratinocytes.
• Only two drug concentrations and a single 48 h time point were tested.

The record

• Journal: International journal of molecular sciences 27(15): 6981
• Published: 2026-08-03
• PMID: 42589634 — DOI: 10.3390/ijms27156981
• MeSH terms: Cells, Cultured, Fibroblasts, Keratinocytes, Skin, Humans, Hydrogen Peroxide, Reactive Oxygen Species, Glucose, Wound Healing, Apoptosis, Cell Proliferation, Cell Survival, Oxidative Stress, Glucagon-Like Peptides, Liraglutide, Semaglutide
• Funding: National and Kapodistrian University of Athens
• Author countries: Greece, Italy

Peptide profiles: Liraglutide.

All indexed evidence: Liraglutide trials & papers.

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