Pharmacology of GLP-1 agonists: describing the therapeutic potential to patients.

The pathophysiology of type 2 diabetes mellitus is complex, consisting of far more physiologic defects than simple insulin resistance and β-cell dysfunction. Our understanding of this progressive disease has moved from a "dual defect" to an "ominous octet" description. This multifactoral concept may explain the difficulty in achieving and maintaining glycemic goals with traditional therapies. Glucagon-like peptide-1 (GLP-1) agonists, which improve insulin secretion, decrease glucagon secretion, increase satiety (and therefore decrease food intake), and may have beneficial effects on β-cell function, represent an important addition to treatment options. Their glucose-dependent mechanism limits the risk for hypoglycemia, and they are associated with weight loss. Glucagon-like peptide-1 agonists may be used alone in patients intolerant of metformin or in combination with metformin, thiazolidinediones, and sulfonylureas (or in any combination therereof). Concomitant use of dipeptidyl-peptidase-4 inhibitors is not recommended because they have a similar basis of action. Current US Food and Drug Administration indications do not include the concomitant use of GLP-1 agonists with insulin.