title: Effect of the glucagon-like peptide-1 analogue liraglutide on coronary microvascular function in patients with type 2 diabetes - a randomized, single-blinded, cross-over pilot study.
abstract: BACKGROUND
  Impaired coronary microcirculation is associated with a poor prognosis in patients with type 2 diabetes. In the absence of stenosis of major coronary arteries, coronary flow reserve (CFR) reflects coronary microcirculation. Studies have shown beneficial effects of glucagon-like peptide-1 (GLP-1) on the cardiovascular system. The aim of the study was to explore the short-term effect of GLP-1 treatment on coronary microcirculation estimated by CFR in patients with type 2 diabetes.
  
  
  METHODS
  Patients with type 2 diabetes and no history of coronary artery disease were treated with either the GLP-1 analogue liraglutide or received no treatment for 10 weeks, in a randomized, single-blinded, cross-over setup with a 2 weeks wash-out period. The effect of liraglutide on coronary microcirculation was evaluated using non-invasive trans-thoracic Doppler-flow echocardiography during dipyridamole induced stress. Peripheral microvascular endothelial function was assessed by Endo-PAT2000®. Interventions were compared by two-sample t-test after ensuring no carry over effect.
  
  
  RESULTS
  A total of 24 patients were included. Twenty patients completed the study (15 male; mean age 57 ± 9; mean BMI 33.1 ± 4.4, mean baseline CFR 2.35 ± 0.45). There was a small increase in CFR following liraglutide treatment (change 0.18, CI95% [-0.01; 0.36], p = 0.06) but no difference in effect in comparison with no treatment (difference between treatment allocation 0.16, CI95% [-0.08; 0.40], p = 0.18). Liraglutide significantly reduced glycated haemoglobin (HbA1c) (-10.1 mmol/mol CI95% [-13.9; -6.4], p = 0.01), systolic blood pressure (-10 mmHg CI95% [-17; -3], p = 0.01) and weight (-1.9 kg CI95% [-3.6; -0.2], p = 0.03) compared to no treatment. There was no effect on peripheral microvascular endothelial function after either intervention.
  
  
  CONCLUSIONS
  In this short-term treatment study, 10 weeks of liraglutide treatment had no significant effect on neither coronary nor peripheral microvascular function in patients with type 2 diabetes. Further long-term studies, preferably in patients with more impaired microvascular function and using a higher dosage of GLP-1 analogues, are needed to confirm these findings.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01931982 .
authors.affiliation: Department of Cardiology, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. rebekkafaber@hotmail.com.|Department of Endocrinology, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. rebekkafaber@hotmail.com.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Faber
authors.affiliation: Department of Endocrinology, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. m.zander@dadlnet.dk.
authors.forename: Mette
authors.initials: M
authors.lastname: Zander
authors.affiliation: Department of Cardiology, Gentofte University Hospital, Kildegårdsvej 28, 2900 Hellerup, Copenhagen, Denmark. atrokmar@gmail.com.
authors.forename: Adam
authors.initials: A
authors.lastname: Pena
authors.affiliation: Department of Cardiology, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. marie.m.michelsen@gmail.com.
authors.forename: Marie M
authors.initials: MM
authors.lastname: Michelsen
authors.affiliation: Department of Cardiology, Rigshospitalet University Hospital, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark. d042195@dadlnet.dk.
authors.forename: Naja D
authors.initials: ND
authors.lastname: Mygind
authors.affiliation: Department of Cardiology, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. Eva.Irene.Bossano.Prescott@regionh.dk.
authors.forename: Eva
authors.initials: E
authors.lastname: Prescott
mesh_terms: D000368:Aged; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D010865:Pilot Projects; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1