A randomized controlled clinical trial has shown that the dipeptidyl peptidase-4 inhibitor sitagliptin may support the healing of diabetic foot ulcers through mechanisms that extend beyond glucose control.
The study compared patients receiving standard conventional therapy alone with those who received sitagliptin in addition to standard care.
The main outcomes examined included ulcer healing, safety, time to healing, changes in circulating endothelial progenitor cells, levels of stromal cell derived factor-1 alpha, and glycosylated hemoglobin. Findings demonstrated that patients treated with sitagliptin experienced greater reductions in ulcer size and overall improvement in wound healing compared to those on conventional therapy alone.
The sitagliptin group also showed an increase in circulating endothelial progenitor cells and higher levels of stromal cell derived factor-1 alpha, suggesting that the drug may enhance vascular repair and tissue regeneration. Notably, there were no differences in long-term blood glucose markers between the groups, indicating that the beneficial effect of sitagliptin on wound healing was independent of its role in glycemic regulation. Safety analysis revealed no adverse events associated with sitagliptin, supporting its tolerability in this patient population.
These results are clinically meaningful because diabetic foot ulcers represent one of the most serious complications of diabetes, often leading to prolonged disability, infection, or amputation. Conventional treatment approaches remain limited in their ability to accelerate wound closure, and the addition of a therapy that can stimulate vascular healing without added safety concerns could offer new hope for patients.
The findings also highlight the therapeutic potential of targeting endothelial progenitor cell mobilization and related pathways in diabetic wound management. While larger trials will be required to confirm these outcomes and to explore long-term implications, this study provides encouraging evidence that sitagliptin may serve as a valuable adjunctive therapy in the treatment of diabetic foot ulcers. By improving wound healing independently of glucose control, sitagliptin underscores the importance of considering pleiotropic benefits of antidiabetic drugs in managing complications of diabetes.
Reference:
W. Gao, D. Chen, H. He, N. Jiang, L. Chen, and X. Ran, “ Sitagliptin, a DPP-4 Inhibitor, Effectively Promotes the Healing of Diabetic Foot Ulcer: A Randomized Controlled Trial,” Journal of Diabetes 17, no. 9 (2025): e70156, https://doi.org/10.1111/1753-0407.70156.
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