Abstract 13747: Addition of Dipeptdyl Peptidase-4 Inhibition to Metformin Mono-therapy Reduces Vascular Inflammation in Humans With Diabetes Mellitus Type 2
Introduction: Endothelial dysfunction precedes the development of atherosclerosis and predicts future adverse cardiovascular events. Systemic endothelial dysfunction is well described in patients with type 2 diabetes (T2DM). Glycemic control that also favorably impacts the vascular endothelium would be an ideal choice for T2DM patients. Prior cell culture and animal work on dipeptdyl peptidase-4 (DPP-4) inhibition suggest these agents could favorably impact human endothelial function. In our study, we looked at the effect of sitagliptin (a DPP4 inhibitor) on endothelial function in T2DM patients on stable metformin therapy.
Methods: Thirty-eight subjects with T2DM who were on a stable dose of metformin were enrolled in a double-blind cross-over trial of sitagliptin (100 mg/day) for eight weeks versus matching placebo. Endothelium dependent vasodilation was measured by percent flow mediated dilatation (FMD) of the brachial artery 2 hours after the 1st dose of sitaglitin and placebo and following 8 weeks of sitagliptin and placebo administration. A 4 week washout period was interposed between treatment periods. Plasma markers for endothelial cell activation, intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) were also measured following chronic dosing of sitagliptin and placebo.
Results: FMD% was not significantly different across all time points (5.6±2.3% pre-sitagliptin 6.3±2.4 post acute sitagliptin, 5.8±2.3 post chronic sitagliptin, 5.2±1.8 pre-placebo, 5.6±2.1 post acute placebo, 6.0±2.9 post chronic placebo, P=0.31 by repeated measures ANOVA). No differences were noted in the hyperemic flow responses as well (P=0.26). Plasma ICAM-1 ( endothelial cell activation ICAM) levels were significantly lower following 8 weeks of sitagliptin compared to placebo [192±70 vs. 228±73 ng/mL (P<0.0001)]. Plasma VCAM-1 was not significantly different following 8 weeks of each treatment [(520±155 vs. 620±96 ng/mL (P=0.67)].
Conclusions: While the addition of DPP-4 inhibition with sitagliptin did not alter endothelium-dependent vasodilation in humans with T2DM on metformin therapy, vascular inflammation may be reduced which could provide an added benefit to these patients.
- Endothelial function
- Diabetes (Type II)
- Inflammation and inflammatory markers
- Drug administration
Author Disclosures: V.K. Puppala: None. A. Branum: None. S. Muhammad: None. J. Wang: None. R. Ying: None. M. Tanner: None. M. Widlansky: Research Grant; Significant; Merck, Sharp & Dohme Corp, NHLBI. Other Research Support; Significant; Everist Health.
- © 2016 by American Heart Association, Inc.