From Glucose to Gauze: A Systematic Review on the Various Wound Healing Properties of DPP ‐4 Inhibitors Beyond Glycaemic Control

Dipeptidyl-peptidase 4 inhibitors, DPP-4i, are an established antiglycaemic medication for Type 2 Diabetes. There has been a growing interest in DPP-4i's potential to improve wound healing and reduce fibrosis. The purpose of this study is to survey the current literature for applications of DPP-4i in wound healing and scars, and explore their potential outside of glycaemic control. A systematic review was performed by three independent reviewers according to PRISMA guidelines using PubMed, SCOPUS, Embase and Cochrane CENTRAL databases. Search terms were synonymous with 'DPP-4i', 'diabetic wounds', 'wound healing', 'scars' and 'skin'. Studies that used DPP-4i in the context of wound healing, scarring, or psoriasis were included for data extraction. A total of 2139 articles were screened, resulting in 31 human, animal and in vitro studies. Human studies showed DPP-4i led to faster wound closure rates, clinical improvement in psoriasis and a reduced risk of keloid formation after sternotomy. In vitro studies reported an increase in cell migration, proliferation and angiogenesis with DPP-4 inhibition. DPP-4i was found to attenuate markers of fibrosis in multiple wound healing models and downregulate TGF-β, pSmad2/3, α-SMA, Col1, Col3 and downstream effectors of the MAPK-NF-κB pathway. This systematic review is the first to summarise and shed light on DPP-4i therapeutic benefits for wound healing and scarring. In multiple in vitro, animal and human studies, DPP-4i have a net positive effect on cutaneous healing. Further studies are needed to reveal the specific molecular pathways through which DPP-4 exerts its effects, particularly in relation to wound healing, scar formation and angiogenesis.