Sitagliptin improves diabetic foot ulcer healing: a randomized controlled trial
Aims: To investigate whether sitagliptin, a DPP-4 inhibitor commonly used for the management of type 2 diabetes, can improve diabetic foot ulcer (DFU) healing when added to standard wound care, and to explore potential biological mechanisms underlying its effects.
Methods: The investigators conducted a randomized controlled trial enrolling patients with diabetic foot ulcers who were allocated to receive either sitagliptin plus conventional wound management or conventional treatment alone. Clinical efficacy was assessed through wound healing outcomes, including ulcer reduction and closure rates. In addition, inflammatory and angiogenic biomarkers were evaluated to provide insight into potential mechanisms involved in tissue regeneration. Safety and tolerability outcomes were also monitored.
Results: Treatment with sitagliptin resulted in significantly greater reduction in ulcer area and improved wound healing compared with standard care alone, with enhanced ulcer closure and greater reductions in wound dimensions. The clinical benefit was accompanied by favorable alterations in biological pathways associated with inflammation regulation and angiogenesis, suggesting that DPP-4 inhibition may influence the complex processes involved in diabetic wound repair. Sitagliptin was well tolerated, with no major safety signals identified.
Conclusions: This randomized clinical trial provides preliminary evidence that sitagliptin may have therapeutic potential as an adjunctive treatment for diabetic foot ulcers possibly through mobilization of CD34+ EPCs in the peripheral blood. The findings support the emerging concept that metabolic therapies may exert clinically relevant effects through mechanisms beyond glucose regulation, opening new avenues for pharmacological approaches to diabetic wound complications.
Comments: The major strength of this study is its randomized controlled design addressing a clinically significant unmet need in diabetic foot care. By combining wound-healing outcomes with biomarker analyses, the authors provide both clinical and mechanistic perspectives supporting the potential role of sitagliptin in tissue repair. The study also highlights an important shift in diabetes therapeutics, from focusing exclusively on glycaemic improvement toward targeting the broader pathophysiological mechanisms contributing to chronic complications.
However, several limitations should be acknowledged. The relatively limited sample size and study population may restrict generalizability across different ethnic groups, healthcare systems, and severity categories of diabetic foot disease. In addition, the study design has several methodological limitations, including inadequate blinding (as this was not a double-blind study), the lack of standardized conventional therapy, and limitations in outcome definition, all of which should be considered when interpreting the results. Furthermore, the follow-up duration does not allow assessment of long-term clinically relevant outcomes, including recurrence, infection-related complications, amputation rates, and patient-reported outcomes. Although biomarker findings support anti-inflammatory and pro-angiogenic effects, the precise molecular mechanisms and their independence from glycaemic improvement remain to be fully established. Future large-scale, multicentre trials should confirm these findings and determine whether sitagliptin can provide sustained clinical benefits as part of comprehensive diabetic foot management.
Eleni Karlafti
Reference. Gao W, Chen D, He H, Jiang N, Chen L, Ran X. Sitagliptin, a DPP-4 Inhibitor, Effectively Promotes the Healing of Diabetic Foot Ulcer: A Randomized Controlled Trial. J Diabetes. 2025 Sep;17(9):e70156. doi: 10.1111/1753-0407.70156. PMID: 40948240; PMCID: PMC12434403.
