Glucagon-like peptide-1 analogs in the treatment of Type 2 diabetes: a review of the Phase II and III trials

Marta Letizia Hribal, Giorgio Sesti

Glucagon-like peptide-1 (GLP-1) analogs-based therapies are a new option for Type 2 diabetes treatment that hold the promise of overcoming the major limitations of traditional treatments, including the increased risk for hypoglycemia and weight gain. GLP-1 is a naturally occurring hormone that potentiates glucose-dependent insulin secretion. The clinical utility of native GLP-1 is, however, limited by its short half-life; these observations led to the generation of GLP-1 analogs, which mimic GLP-1 action in vivo in humans. Here, we review the data from clinical trials that have assessed mechanism of action, efficacy and safety of GLP-1 agonists; these trials have demonstrated the efficacy of GLP-1 analogs in reducing glycosylated hemoglobin and fasting plasma glucose levels. The use of these drugs was associated with weight loss and reductions in blood pressure, with a low risk of hypoglycemia, GLP-1 agonists were generally well tolerated with the most frequent adverse effects being nausea.