Glucagon-like peptide receptor agonists and dipeptidyl peptidase-4 inhibitors in the treatment of diabetes: a review of clinical trials

PURPOSE OF REVIEW: To discuss the virtues and shortcomings of the glucagon-like peptide-1 receptor agonists and the dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes.

RECENT FINDINGS: The injectable glucagon-like peptide-1 receptor agonists exenatide significantly improves glycaemic control, with average reductions in haemoglobin A1c of about 1.0%, fasting plasma glucose of about 1.4 mmol/l, and causes a weight loss of approximately 2-3 kg after 30 weeks of treatment in patients with type 2 diabetes. The adverse effects are transient nausea and vomiting. The long-acting glucagon-like peptide-1 receptor agonists liraglutide and exenatide long-acting release reduce haemoglobin A1c by about 1.0-2.0% and have fewer gastrointestinal side-effects. The orally available dipeptidyl peptidase-4 inhibitors, that is sitagliptin and vildagliptin reduce haemoglobin A1c by 0.5-1.0%, are weight neutral and without gastrointestinal side-effects.

SUMMARY: The benefits and position of the glucagon-like peptide-1 analogues and the dipeptidyl peptidase-4 inhibitors in the diabetes treatment algorithm will be clarified when we have long-term trials with hard cardiovascular endpoints and data illustrating the effects on the progression of type 2 diabetes.