Recently incretin-based therapies have been developed in the clinical practice, this class includes both the
dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin), and the glucagon-like peptide-
1 (GLP-1) receptor agonists [exenatide, exenatide long acting release (LAR) and liraglutide].
In particular exenatide and liraglutide have structural similarity and bind to the GLP-1 receptor, displaying a similar broad
range of activities relevant to improving glycemic control, including stimulation of insulin secretion and reduction of
glucagon secretion, both in a glucose-dependent manner. Furthermore, GLP-1 slows gastrointestinal motility and
increases satiety, reducing the food intake; it also promotes β-cell proliferation and probably neogenesis, while reducing
apoptosis in animal models.
We conducted a review analyzing clinical efficacy and safety of GLP-1 receptor agonists exenatide and liraglutide, both
alone and in combination with other anti-diabetic drugs, including the most important studies about them in the latest
We concluded that GLP-1 receptor agonists appear to be a good choice to decrease HbA1c levels and to lower postprandial
blood glucose levels. They also suppress glucagon secretion and slow gastric motility. They also have positive
effects on β-cell function and they gave a significant decrease of body weight. They are not associated with
hypoglycemia, but cause a relatively high frequency of gastrointestinal disturbances, with some patients experiencing one
or more episodes of nausea, vomiting, or diarrhea. However, after an evaluation of the advantages and the disadvantages,
we concluded that, once metformin fails to reach an adequate glycemic control, GLP-1 receptor agonists can be a valid
alternative, especially in obese type 2 diabetic patients. GLP-1 receptor agonists should be considered also in patients in
therapy with metformin and another agent, such as a sulfonylurea, because of the minor risk of developing hypoglycemia
and the positive effect on body weight.