Role of Dipeptidyl Dipeptidase 4 Inhibitors in the Management of Diabetic Foot

Background: Patients with diabetes mellitus face difficulties in wound healing. It is important to explore therapeutic options for diabetic complications such as ulcers. This study evaluates the role of dipeptidyl dipeptidase 4 inhibitors (DPP4i) in the management of diabetic foot. Methods: Literature search was conducted in electronic databases (Google Scholar, Ovid, PubMed, Science Direct, and Springer) and studies were selected for inclusion if they reported the incidence rate of diabetic foot ulcer during DPP4i treatment or evaluated the effect of DPP4i on wound healing. Incidence rates of foot ulcer, amputation and peripheral vascular disease were pooled to achieve overall estimates. Meta-analyses of odds ratios were performed to evaluate the risk of foot ulcer, amputation, and peripheral vascular disease with DPP4i, and to examine the effect of DPP4i treatment on ulcer healing. Results: Ten studies (532354 DPP4i and 2092010 non-DPP4i treated diabetes patients) were included. Incidence rates of foot ulcer, amputation, and peripheral vascular disease were 3.80 [95% confidence interval (CI): 0.22, 7.39], 0.82 [95%CI: 0.60, 1.05], and 22.33 [95%CI: 9.14, 35.53] per 1000 person-years respectively in patients treated with DPP4i and 3.60 [95%CI: 1.77, 5.39], 0.76 [95%CI: 0.58, 0.94], and 20.9 [95%CI: 16.04, 25.81] per 1000 person-years respectively in patients treated with non-DPP4i drugs. Risk of ulcer or amputation with DPP4i was not consistent across studies. Odds of non-healing of ulcer were significantly lower with DPP4i in comparison with controls (odds ratio: 0.27 [95%CI: 0.10, 0.71]; p = 0.008). Conclusion: Incidence rates of diabetic foot and amputation are found to be similar with DPP4i and non-DPP4i drugs. DPP4i improved wound healing of diabetic foot in 3-month randomized trials.