Effects of Galvus (Vildagliptin) on Markers of Inflammation in Diabetic Foot Ulcer: A prospective, randomized, double-blind, placebo-controlled pilot study

Diabetic patients are at a particularly high risk for poor wound healing in general and foot ulcer in particular. The lifetime risk for developing chronic foot ulcer has been estimated to reach about 15-20% (1). Despite considerable advances in diabetic care, foot ulcers continue to be responsible for a high number of lower limb amputations that are associated with decrease in quality of life and increased risk of mortality (2). The major risk factors for diabetic foot ulcer (DFU) are polyneuropathy and peripheral vascular disease. Diabetes induces complex vascular changes, promoting accelerated atherosclerosis and hypercoagulability complicating foot ulcer which can be assessed indirectly by a number of inflammatory markers. Animal studies have suggested numerous beneficial anti-inflammatory effects of dipeptidyl peptidase-4 inhibitors (DPP4i), well beyond the effects on blood glucose alone (3). Interestingly, investigation on anti-inflammatory property of DPP4i-vildagliptin in human setting is scanty (4). Treatment with a DPP4i may offer an attractive blood glucose reduction with synergistic mechanism of action while exerting additional wound healing properties. Reduction of inflammatory marker levels is of great clinical importance and may correlate with improvement of diabetic wound healing. Therefore, in the present study we plan to focus on possible anti inflammatory properties of DPP4i in subjects with DFU. Primary objective: To demonstrate that Vildagliptin therapy is associated with clinically significant reduction in biological markers of inflammation compared to placebo in patients with DFU. Our Primary aim is demonstration of a significant (= 20%) reduction in the serum levels of interleukin 6 (IL-6). Secondary objectives: Partial or complete closure of foot ulcer or improvement in other biological markers of inflammation including: hs-CRP, platelet reactivity testing, TNF-alpha, interleukin 1 beta (IL-1 beta), adiponectin and tissue TGF- beta-1 levels. References 1. Lavery LA, et al. Diabetes Care. 2006:1288. 2. Singh N, et al. JAMA 2005: 293:217. 3. Shah Z, et al. Circulation. 2011: 124:2338. 4. Rizzo MR, et al. Diabetes Care. 2012: 35:2076.