Vildagliptin reduces plasma stromal cell‐derived factor‐1α in patients with type 2 diabetes compared with glimepiride

Abstract

Aims/IntroductionDipeptidyl peptidase‐4 inhibitors might have pleiotropic protective effects on cardiovascular disease (CVD), in contrast to sulfonylureas. Therefore, we compared various CVD risk factors between vildagliptin and glimepiride.Materials and MethodsWe carried out a randomized, prospective and crossover trial. A total of 16 patients with type 2 diabetes whose glycated hemoglobin was >7% were randomized to add vildagliptin or glimepiride. After 12‐week treatment, each drug was replaced with the other for another 12 weeks. Before and after each treatment, glucose homeostasis and CVD risk factors were assessed, and the continuous glucose monitoring system was applied to calculate glycemic variability.ResultsThe mean age of the participants was 60 years, 31% were men, body mass index 25.5 kg/m2 and HbA1c 8.41%. Both vildagliptin and glimepiride significantly decreased glycated hemoglobin and glycemic variability indices. Despite the improved glucose homeostasis, favorable change of CVD markers was not prominent in both the arms, along with significant weight gain. Only plasma stromal cell‐derived factor (SDF)‐1α decreased by 30% in the vildagliptin arm. According to regression analyses, the reduction of SDF‐1α was independently associated with vildagliptin usage and serum interleukin‐6 changes, but white blood cells were not related with the SDF‐1α changes.ConclusionCompared with glimepiride, vildagliptin arrestingly decreased plasma SDF‐1α, and its clinical implications should be further investigated.

The Oral Dipeptidyl-Peptidase-4 Inhibitor Sitagliptin Increases Circulating Levels Of Stromal-Derived Factor-1 Alpha

“…In two recent studies, vildalgliptin treatment significantly reduced (C-term) SDF-1α plasma levels [20,21]. At variance with our results, Aso et al [22] found that sitagliptin decreased SDF-1a levels compared with glimepiride.…”

“…This study has shown that sitagliptin therapy has a favourable effect on SDF-1α levels. Of note, various effects of DPP-4 therapy on SDF-1α levels have hitherto been reported [15][16][17][18][19][20][21][22]. A small clinical trial showed that sitagliptin therapy significantly increased EPCs and SDF-1α [9].…”

Multiple limb compartment syndrome as a manifestation of capillary leak syndrome secondary to metformin and dipeptidyl peptidase IV inhibitor overdose

“…Interestingly, plasma SDF-1α decreased with the effect of vildagliptin, which seems to be a converse effect of DPP-4 inhibitors on SDF-1α. Although the reason is unclear, this finding is consistent with a previous report [ 14 ] and may occur only with vildagliptin. The minimum level of plasma SDF-1α is on day 2, which is consistent with the pharmacokinetics of vildagliptin that the estimated volume of distribution is high (71 L) and that the fraction bound to proteins is relatively low (9.3%).…”

Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

“…In the Framingham Heart Study of 3359 participants (10% of individuals with diabetes), high plasma SDF-1α were directly and independently associated with the risk of heart failure and 10-year all-cause mortality [56]. Two independent randomized double-blind control studies [14,32] in small groups of DM2 patients provide interesting evidence for the effect of vildagliptin on SDF-1α. Although DPP-4 degrades SDF-1α and its blockade should be associated with an increase in SDF-1α, the administration of vildagliptin resulted in a significant decrease in circulating SDF-1α.…”