Liraglutide benefits overall CV risk profile in diabetes

2 February 2012

MedWire News: In patients with diabetes that is well controlled with metformin monotherapy, the addition of liraglutide improves several cardiovascular (CV) risk factors beyond glycemic control, suggest study findings.

“This study is the first to show an improvement in several CV risk markers in patients with Type 2 diabetes already well controlled on metformin therapy,” write Thomas Forst (Institute for Clinical Research and Development, Mainz, Germany) and colleagues in Diabetic Medicine.

The researchers say that growing lines of evidence indicate a physiologic signaling of glucagon-like peptide-1 (GLP-1) on endothelium and vascular smooth muscle cells.

In addition, several recent studies indicate that liraglutide treatment in patients with Type 2 diabetes does not only improve metabolic parameters, but might also have beneficial effects on the overall CV risk profile, they say.

The team therefore investigated the endothelial and vascular effects of adding liraglutide to ongoing metformin treatment in 40 patients with well-controlled Type 2 diabetes.

The patients were randomly allocated to receive additional liraglutide (liraglutide group, n=21) over 12 weeks or remain on metformin therapy alone (metformin group, n=19). Liraglutide treatment was initiated at 0.6 mg per day, increasing to 1.2 mg after week 1, and to 1.8 mg after week 6.

Assessment of vascular stiffness, retinal endothelial function, and fasting blood glucose was performed at baseline, 6 weeks, and 12 weeks.

The researchers found that, at 12 weeks, fasting glucose levels, glycated hemoglobin (HbA1c), and body weight had declined in the patients receiving liraglutide, whereas they remained unchanged in the patients who stayed on metformin alone. Specifically, mean fasting glucose levels fell from 7.21 mmol/L to 6.47 mmol/L, HbA1c from 6.32% to 5.77%, and body weight from 93.2 kg to 89.7 kg in the liraglutide group.

The authors also found that markers of endothelial function, asymmetric dimethylarginine, E-selectin, and plasminogen activator inhibitor 1 (PAI-1) significantly decreased in the liraglutide group by the end of the study, compared with those in the metformin group.

In addition, retinal endothelial response (assessed using scanning laser Doppler flowmetry before and after flicker light stimulation) increased from 7.0% to 11.1% in the liraglutide group, whereas it decreased from 15.7% to 13.0% in the metformin group.

Furthermore, a linear correlation was observed between reduction in body weight and PAI-1, and E-selectin levels, report the authors.

“Therefore it could be considered that the observed pleiotropic effects of liraglutide might be assigned to changes in the activity of the adipose tissue rather than to an improvement in blood glucose control,” they say.

“The observed results strengthen the hypothesis of beneficial CV effects of liraglutide that go beyond glycemic control,” conclude Forst and team.

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Diabet Med 2012; Advance online publication