title: Effect of Linagliptin on Vascular Function: A Randomized, Placebo-controlled Study.
abstract: The dipeptidyl peptidase-4 inhibitor, linagliptin, possesses pleiotropic vasodilatory, antioxidant, and anti-inflammatory properties in animals, independent of its glucose-lowering properties. Although large, randomized clinical trials are being conducted to better evaluate the efficacy and safety of linagliptin on cardiovascular outcomes, little is known about its effects on vascular function in humans.
  
  
  
  This study sought to evaluate the effect of linagliptin on surrogates of vascular and mitochondrial function.
  
  
  
  This was a randomized, double-blind, placebo-controlled trial at a tertiary care center with a large type 2 diabetes referral base.
  
  
  
  Forty participants with type 2 diabetes were included in a 12-wk treatment of either linagliptin 5mg/d or placebo.
  
  
  
  Micro- and macrovascular functions were assessed using laser Doppler coupled with iontophoresis and with brachial flow-mediated dilation, respectively. Mitochondrial function was assessed by phosphorus-31 metabolites changes in the calf muscle measured by magnetic resonance spectroscopy. Circulating endothelial progenitor cells, as well as inflammatory cytokines, growth factors, and biomarkers of endothelial function were also quantified.
  
  
  
  Linagliptin was associated with an increase in axon reflex-dependent vasodilation, a marker of neurovascular function (P = .05). A trend indicating increased endothelium-dependent microvascular reactivity was observed (P = .07). These were associated with decreases in concentrations of IFNγ (P < .05), IL-6 (P = .03), IL-12 (P < .03), and MIP-1 (P < .04) following linagliptin treatment when compared with placebo.
  
  
  
  This study demonstrates that linagliptin tends to improve endothelial and neurovascular microvascular function and is associated with decreased markers of inflammation in patients with type 2 diabetes. There was no significant effect of linagliptin on mitochondrial function, macrovascular function, or endothelial progenitor cells.
authors: Microcirculatory Laboratory and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115.
authors: Dimitrios
authors: D
authors: Baltzis
authors: Microcirculatory Laboratory and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115.
authors: Jody R
authors: JR
authors: Dushay
authors: Microcirculatory Laboratory and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115.
authors: Jordan
authors: J
authors: Loader
authors: Microcirculatory Laboratory and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115.
authors: Jim
authors: J
authors: Wu
authors: Microcirculatory Laboratory and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115.
authors: Robert L
authors: RL
authors: Greenman
authors: Microcirculatory Laboratory and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115.
authors: Matthieu
authors: M
authors: Roustit
authors: Microcirculatory Laboratory and Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115.
authors: Aristidis
authors: A
authors: Veves
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000069476:Linagliptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care; D014652:Vascular Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D000069476:Linagliptin