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.