Non-glycaemic effects mediated via GLP-1 receptor agonists and the potential for exploiting these for therapeutic benefit: focus on liraglutide.

The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) liraglutide and exenatide can improve glycaemic control by stimulating insulin release through pancreatic β-cells in a glucose-dependent manner. GLP-1 receptors are not restricted to the pancreas; therefore, GLP-1 RAs cause additional non-glycaemic effects. Preclinical and clinical trial data suggest a multitude of additional beneficial effects related to GLP-1 RA therapy, including improvements in β-cell function, systolic blood pressure and body weight. These effects are of a particular advantage to patients with type 2 diabetes, as most are affected by β-cell dysfunction, obesity and hypertension. Transient gastrointestinal adverse events, such as nausea and diarrhoea, are also common. To improve gastrointestinal tolerability, an incremental dosing approach is used with liraglutide and exenatide twice daily. A potential protective role for GLP-1 RAs in the cardiovascular and central nervous systems has been suggested from animal studies and short-term clinical trials. These effects and other safety aspects of GLP-1 therapy are currently being investigated in ongoing long-term clinical studies.