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

Cardiovascular Diabetology

Eva Prescott¹  Naja D Mygind³  Marie M Michelsen¹  Adam Pena⁴  Mette Zander²  Rebekka Faber² 

[1] Department of Cardiology, Bispebjerg University Hospital, Bispebjerg Bakke 23, Copenhagen NV, 2400, Denmark;Department of Endocrinology, Bispebjerg University Hospital, Copenhagen NV, 2400, Denmark;Department of Cardiology, Rigshospitalet University Hospital, Blegdamsvej 9, Copenhagen Ø, 2100, Denmark;Department of Cardiology, Gentofte University Hospital, Kildegårdsvej 28, 2900 Hellerup, Copenhagen, Denmark

关键词: Cross-over design;    Intervention study;    Liraglutide;    Endothelial function;    Microvascular dysfunction;    Coronary flow reserve;    Glucagon-like peptide-1;    Type 2 diabetes;    Diabetes Mellitus;    Coronary microcirculation;   

Others  :  1177359
DOI  :  10.1186/s12933-015-0206-3

 received in 2015-01-01, accepted in 2015-03-27,  发布年份 2015

【 摘 要 】

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.

Trial registration

ClinicalTrials.gov: NCT01931982 webcite.

【 授权许可】

   
2015 Faber et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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