Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy
| Autor: | Tisha M Suboc, Amberly Branum, Jingli Wang, Kara Signorelli, Rong Ying, Venkata K. Puppala, Michael E. Widlansky, Mobin Malik, Sudhi Tyagi, Michael J Tanner |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male medicine.medical_specialty Time Factors Endothelium Dipeptidyl Peptidase 4 Vascular Cell Adhesion Molecule-1 030209 endocrinology & metabolism Inflammation Type 2 diabetes 030204 cardiovascular system & hematology Article Nitric oxide 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Wisconsin Double-Blind Method Internal medicine medicine Humans Dipeptidyl peptidase-4 Aged Dipeptidyl-Peptidase IV Inhibitors Cross-Over Studies business.industry Sitagliptin Phosphate Middle Aged medicine.disease Intercellular Adhesion Molecule-1 Metformin Vasodilation medicine.anatomical_structure Endocrinology Treatment Outcome chemistry Diabetes Mellitus Type 2 Cell culture Sitagliptin Drug Therapy Combination Female Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine business Biomarkers medicine.drug |
| Zdroj: | Vascular medicine (London, England). 22(3) |
| ISSN: | 1477-0377 |
| Popis: | Cell culture and animal work indicate that dipeptidyl peptidase-4 (DPP-4) inhibition may exert cardiovascular benefits through favorable effects on the vascular endothelium. Prior human studies evaluating DPP-4 inhibition have shown conflicting results that may in part be related to heterogeneity of background anti-diabetes therapies. No study has evaluated the acute response of the vasculature to DPP-4 inhibition in humans. We recruited 38 patients with type 2 diabetes on stable background metformin therapy for a randomized, double-blind, placebo-controlled crossover trial of DPP-4 inhibition with sitagliptin (100 mg/day). Each treatment period was 8 weeks long separated by 4 weeks of washout. Endothelial function and plasma markers of endothelial activation (intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)) were measured prior to and 2 hours following acute dosing of sitagliptin or placebo, as well as following 8 weeks of intervention with each pill. Thirty subjects completed the study and were included in analyses. Neither acute nor chronic sitagliptin therapy resulted in significant changes in vascular endothelial function. While post-acute sitagliptin ICAM-1 levels were lower than that post-chronic sitagliptin, the ICAM-1 concentration was not significantly different than pre-acute sitagliptin levels or levels measured in relationship to placebo. There were no significant changes in plasma VCAM-1 levels at any time point. Acute and chronic sitagliptin therapies have neutral effects on the vascular endothelium in the setting of metformin background therapy. In conclusion, our findings suggest DPP-4 inhibition has a neutral effect on cardiovascular risk in patients without a history of heart failure or renal insufficiency. Trial Registration: NCT01859793 |
| Databáze: | OpenAIRE |
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