Diabetes and obesity are associated with vascular dysfunction (e.g. capillary rarefaction) and an increased risk of vascular complications of both large blood vessels (macrovasculature) (e.g. cardiovascular disease) and small vessels (microvasculature) (e.g. diabetic retinopathy). There is an unmet need for better preventative and therapeutic strategies for these vascular complications. One such avenue maybe incretin based medications, for example dipeptidyl peptidase-IV inhibitors (DPP-IVi) such as vildaglitpin and sitagliptin, that are already licenced to aid glycaemic control in type 2 diabetes. DPP-IVi slow the breakdown of endogenous incretins (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide) thereby prolonging their insulin releasing action.  There is interest in their non-glycaemic effects, particularly whether they have favourable effects on the cardiovascular system, and thus have beneficial effects in individuals at higher risk of vascular disease / dysfunction.  The majority of previous research has focused on the macrovascular effects of incretin based medications and little is known about the potential microvascular effects of these therapies, particularly the DPP-IVi in humans, in vivo. This study examined whether short term DPP-IV inhibition with vildagliptin alters micro- and macrovascular function in obese men. Study design: Crossover, randomised double-blind placebo-controlled study. Method: 15 obese men were recruited (age range:28-72years). Following recruitment participants were randomised to vildagliptin (50mg twice daily) or placebo for 12 weeks. At the end of the treatment period, microvascular (dermal capillary density; maximum hyperaemia; endothelial (in)dependent microvascular function; microvascular filtration capacity; peak reactive hyperaemia) and macrovascular assessments (flow mediated dilatation of the brachial artery and applanation tonometry) were performed. Following a 4 week washout period the participant received the alternative treatment for 12 weeks. Vascular assessments were repeated within the last 2 weeks of treatment. The study was approved by local NHS Research Ethics Committee (REC number: 09/H0206/33). Written, informed consent was obtained from all participants. Results: 14 participants completed the study. Active treatment resulted in a small but significant reduction in HbA1c (active mean ± standard deviation: 38.1±4.8 vs placebo: 39.1±4.1mmol/mol, p=0.003 paired T-test). Maximal dermal capillary density was increased with DPP-IV inhibition (active median (25th,75th centiles) 129 (118,158) mm2 vs placebo: 122 (111,139) mm2, p=0.018 Wilcoxon Signed Rank test). There was no significant change in other vascular assessments. Ongoing in vitro experiments are exploring this area further by examining the impact of DPP-IV inhibition on proliferation, migration and angiogenic tube formation of human microvascular endothelial cells. Preliminary results suggest that sitagliptin (1µM) significantly increases endothelial cell proliferation as assessed by BrdU (DNA) incorporation (331.6 ± 10.4% vs control (100%), p<0.01 Mann-Whitney U test, n = 9) and DNA staining (135.4 ± 6.5% vs control (100%), p<0.01, n = 6). Discussion: DPP-IV inhibition with vildagliptin, increased maximal dermal capillary density in obese men. Preliminary data also suggests that DPP-IV inhibition increases microvascular endothelial cell proliferation in vitro. Further work is required to explore these potential pro-angiogenic actions of DPP-IVi and their underlying mechanisms.