Effect of liraglutide on body weight and microvascular function in non-diabetic overweight women with coronary microvascular dysfunction

BACKGROUND: Coronary microvascular dysfunction (CMD) is associated with adverse cardiovascular outcomes and CMD is a hallmark of type 2 diabetes. Liraglutide improves cardiovascular prognosis through partly unknown mechanisms. We hypothesized that treatment with liraglutide improves CMD and symptoms through weight loss, in non-diabetic overweight patients with angina and no obstructive coronary artery disease (CAD).

METHODS: We included 33 non-diabetic overweight women (BMI > 25) with CMD (Coronary flow velocity reserve (CFVR) ≤2.5), angina symptoms and no obstructive CAD, in an open-label proof-of-concept study. The protocol included a control period of 5 weeks followed by an intervention period with liraglutide aiming at 3 mg daily for 12 weeks. Participants were investigated before and after the control period and again 1-2 weeks after last liraglutide dose. Primary outcomes were change in CFVR and change in angina symptoms measured by the Seattle Angina Questionnaire (SAQ) in the intervention period compared with the control period. (clinicaltrials.gov, NCT02602600, and ethically approved).

RESULTS: Twenty-nine participants completed the study. Liraglutide treatment led to a significant weight loss (mean 6.03 kg (95%CI: 5.22;6.84)) and decrease in systolic blood pressure (mean 10.95 mm Hg (95%CI: 4.60;17.30)). Baseline median CFVR was 2.30 (IQR 1.91;2.51) and remained unchanged after liraglutide treatment (mean change 0.07 (95%CI: -0.07;0.21)). There were no effects on symptoms measured by SAQ or parameters of left ventricular systolic as well as diastolic function.

CONCLUSIONS: Treatment with liraglutide led to significant weight loss and lowering of blood pressure with no concomitant symptoms alleviation during treatment and no improvement in coronary microvascular function.