Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with insulinotropic
properties. Apart from the glycemic actions, cardiovascular effects by GLP-1 have recently
been reviewed. Receptors for GLP-1 are expressed in the rodent and human heart and acute
activation of GLP-1 signalling has been shown to influence e.g. heart rate and blood
pressure. In a knock-out mouse model, GLP-1R-/- mice exhibited a defective cardiovascular
contractile response together with left ventricular hypertrophy. GLP-1 improves severe left
ventricular heart failure in humans suffering from a myocardial infarction. Hence, it has
been demonstrated that GLP-1 exerts direct functional effects through both GLP-1 receptor
dependent and independent pathways in the heart.
Native GLP-1 is an extremely short acting peptide, with a half-time breakdown of 1-2 minutes,
a feature that makes it unsuitable as a drug treatment for type 2 diabetes. To this end,
several long-acting GLP-1 analogues, drugs for treating type 2 diabetes, have been tested for
this purpose. The analogue liraglutide exerts its effects via the native GLP-1 receptor,
localized not only on the pancreatic β-cells, but also in the human heart. Interestingly,
liraglutide has been demonstrated to have beneficial effect on heart function in mice. Taken
together, recent data shows that GLP-1 and its stable analogue liraglutide exert beneficial
cardiovascular effects.
The purpose of this study is to determine whether the glucagon-like peptide-1 (GLP-1)
analogue liraglutide improves heart function (measured as left ventricle longitudinal
function and/or functional reserve during rest and/or after exercise) after 18 weeks of
liraglutide + metformin, compared with glimepiride + metformin, using tissue Doppler
echocardiography.