title: GLP-1-Based Therapies Have No Microvascular Effects in Type 2 Diabetes Mellitus: An Acute and 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.
abstract: To assess the effects of glucagon-like peptide (GLP)-1-based therapies (ie, GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) on microvascular function in patients with type 2 diabetes mellitus.
  
  
  
  We studied 57 patients with type 2 diabetes mellitus (mean±SD age: 62.8±6.9 years; body mass index: 31.8±4.1 kg/m(2); HbA1c [glycated hemoglobin] 7.3±0.6%) in an acute and 12-week randomized, placebo-controlled, double-blind trial conducted at the Diabetes Center of the VU University Medical Center. In the acute study, the GLP-1 receptor agonist exenatide (therapeutic concentrations) or placebo (saline 0.9%) was administered intravenously. During the 12-week study, patients received the GLP-1 receptor agonist liraglutide (1.8 mg daily), the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg daily), or matching placebos. Capillary perfusion was assessed by nailfold skin capillary videomicroscopy and vasomotion by laser Doppler fluxmetry, in the fasting state and after a high-fat mixed meal. In neither study, treatment affected fasting or postprandial capillary perfusion compared with placebo (P>0.05). In the fasting state, acute exenatide infusion increased neurogenic vasomotion domain power, while reducing myogenic domain power (both P<0.05). After the meal, exenatide increased endothelial domain power (P<0.05). In the 12-week study, no effects on vasomotion were observed.
  
  
  
  Despite modest changes in vasomotion, suggestive of sympathetic nervous system activation and improved endothelial function, acute exenatide infusion does not affect skin capillary perfusion in type 2 diabetes mellitus. Twelve-week treatment with liraglutide or sitagliptin has no effect on capillary perfusion or vasomotion in these patients. Our data suggest that the effects of GLP-1-based therapies on glucose are not mediated through microvascular responses.
authors: From the Diabetes Center, Department of Internal Medicine (M.M.S., L.T., M.H.A.M., M.H.H.K., M.D., E.H.S., D.H.v.R.) and Department of Epidemiology and Biostatistics (T.H.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands (T.H.). mm.smits1@vumc.nl.
authors: Mark M
authors: MM
authors: Smits
authors: From the Diabetes Center, Department of Internal Medicine (M.M.S., L.T., M.H.A.M., M.H.H.K., M.D., E.H.S., D.H.v.R.) and Department of Epidemiology and Biostatistics (T.H.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands (T.H.).
authors: Lennart
authors: L
authors: Tonneijck
authors: From the Diabetes Center, Department of Internal Medicine (M.M.S., L.T., M.H.A.M., M.H.H.K., M.D., E.H.S., D.H.v.R.) and Department of Epidemiology and Biostatistics (T.H.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands (T.H.).
authors: Marcel H A
authors: MH
authors: Muskiet
authors: From the Diabetes Center, Department of Internal Medicine (M.M.S., L.T., M.H.A.M., M.H.H.K., M.D., E.H.S., D.H.v.R.) and Department of Epidemiology and Biostatistics (T.H.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands (T.H.).
authors: Trynke
authors: T
authors: Hoekstra
authors: From the Diabetes Center, Department of Internal Medicine (M.M.S., L.T., M.H.A.M., M.H.H.K., M.D., E.H.S., D.H.v.R.) and Department of Epidemiology and Biostatistics (T.H.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands (T.H.).
authors: Mark H H
authors: MH
authors: Kramer
authors: From the Diabetes Center, Department of Internal Medicine (M.M.S., L.T., M.H.A.M., M.H.H.K., M.D., E.H.S., D.H.v.R.) and Department of Epidemiology and Biostatistics (T.H.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands (T.H.).
authors: Michaela
authors: M
authors: Diamant
authors: From the Diabetes Center, Department of Internal Medicine (M.M.S., L.T., M.H.A.M., M.H.H.K., M.D., E.H.S., D.H.v.R.) and Department of Epidemiology and Biostatistics (T.H.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands (T.H.).
authors: Erik H
authors: EH
authors: Serné
authors: From the Diabetes Center, Department of Internal Medicine (M.M.S., L.T., M.H.A.M., M.H.H.K., M.D., E.H.S., D.H.v.R.) and Department of Epidemiology and Biostatistics (T.H.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands (T.H.).
authors: Daniël H
authors: DH
authors: van Raalte
mesh_terms: D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D017078:Laser-Doppler Flowmetry; D000069450:Liraglutide / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D020678:Microscopic Angioscopy; D018715:Microscopy, Video; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D009426:Netherlands; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D012039:Regional Blood Flow; D015398:Signal Transduction / Q000187:drug effects; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D012867:Skin / Q000098:blood supply*; D013997:Time Factors; D016896:Treatment Outcome; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D054795:Incretins; D000069450:Liraglutide; D010455:Peptides; D000068900:Sitagliptin Phosphate; D014688:Venoms; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human; C042807:DPP4 protein, human
keywords: DPP-4 inhibitors; GLP-1 receptor agonists; blood pressure; diabetes mellitus; microcirculation