Dulaglutide accelerated wound healing in diabetic mice by activating the Nrf2 pathway to prevent ferroptosis, a form of iron-dependent cell death caused by high blood sugar.
Ferroptosis reversed by dulaglutideHigh glucose-induced iron overload, oxidative stress, and cell death in wound cells were all reversed by dulaglutide through Nrf2 pathway activation
What the researchers found
In db/db diabetic mice with full-thickness wounds, dulaglutide delivered via subcutaneous injection around the wound:
- Increased VEGF expression and Ki67 proliferation marker, accelerating wound closure
- In vitro, promoted keratinocyte (HaCaT cell) proliferation and migration under high glucose conditions
- High glucose induced ferroptosis markers: increased Fe²⁺, ROS, and MDA; decreased GSH and SOD
- Dulaglutide reversed all ferroptosis markers
- Mechanism: dulaglutide activated Nrf2 signaling, increasing Gpx4 and Slc7a11 expression to inhibit ferroptosis
- Results consistent in both in vivo (mouse wounds) and in vitro (cell culture) models
Why it matters
Diabetic wounds are a massive clinical problem — they precede most non-traumatic amputations. This study reveals that ferroptosis (iron-dependent cell death) is a key mechanism in delayed diabetic wound healing and that a GLP-1 drug can specifically counteract it. Since dulaglutide is already FDA-approved for diabetes, repurposing it for wound healing could be relatively straightforward clinically.
How the study worked
Full-thickness wounds were created on db/db diabetic mice, and dulaglutide was injected subcutaneously around the wound perimeter. Wound closure rates were monitored over time. In vitro, HaCaT keratinocytes were treated with dulaglutide under high glucose conditions. Cell viability was assessed by CCK-8 and EdU assays. Ferroptosis was evaluated by measuring Fe²⁺, ROS, MDA, GSH, SOD levels, and ferroptosis marker expression. Nrf2 pathway activation was confirmed by protein expression analysis.
What this study cannot tell us
This was a preclinical study in genetically diabetic mice, which may not fully represent human diabetic wound healing. The dulaglutide was injected around the wound rather than given systemically, so the local versus systemic contribution is unclear. Long-term effects and optimal dosing for wound healing were not assessed. The study did not compare dulaglutide to other GLP-1 drugs previously shown to promote wound healing.
How to read the evidence
This is a preclinical study using a genetically diabetic mouse model with complementary in vitro cell culture experiments. The mechanistic insights are strong, but no human wound healing data is presented.
When this study was published
Published in 2025, this is very recent research adding to the evidence that GLP-1 drugs have wound-healing properties beyond their primary diabetes indication.
The bigger picture
Ferroptosis is an emerging area of research across multiple diseases. This study is among the first to link GLP-1 receptor activation to ferroptosis inhibition in wound healing. Combined with growing evidence that GLP-1 drugs have wound-healing, anti-inflammatory, and tissue-protective effects, this work supports the expanding therapeutic potential of GLP-1 agonists far beyond blood sugar control.
Questions still open
- Would systemic dulaglutide treatment (standard injection site) also improve wound healing in diabetic patients?
- How does dulaglutide's wound-healing effect compare to exendin-4 and liraglutide, which have also shown wound benefits?
- Could topical GLP-1 formulations be developed specifically for diabetic wound care?
Common questions
What is ferroptosis and why does it matter for diabetic wounds?
Could GLP-1 drugs help heal diabetic wounds?
Read the original research
Dulaglutide accelerates diabetic wound healing by suppressing Nrf2-dependent ferroptosis in diabetic mice.
Peptides, 185, 171366
Citation
Xi, Liuqing; Du, Juan; Lu, Yan; Xue, Wen; Xia, Yuxuan; Chen, Tingxu; Xiao, Yang; Xu, Nuo; Wang, Yansheng; Gao, Jianfang; Li, Wenyi; Huang, Shan. (2025). Dulaglutide accelerates diabetic wound healing by suppressing Nrf2-dependent ferroptosis in diabetic mice.. Peptides, 185, 171366. https://doi.org/10.1016/j.peptides.2025.171366