Overview of glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors for type 2 diabetes.
BACKGROUND
Impairment of incretin activity is now recognized as integral to the metabolic derangement underlying type 2 diabetes. Glucoregulatory agents that target the incretin system have recently been developed, and the place of these drugs in the treatment of type 2 diabetes can be assessed based on a growing body of clinical data.


METHODS
A PubMed search was conducted to identify clinical studies of incretin therapies in type 2 diabetes. Article reference lists were also searched for relevant information, and supplemental material such as conference abstracts, drug prescribing information, and treatment guidelines were included as appropriate.


RESULTS
Two classes of therapies target the incretin system. The first, glucagon-like peptide-1 (GLP-1) agonists (exemplified by exenatide and liraglutide), have demonstrated considerable efficacy in clinical trials, reducing hemoglobin A1c (HbA1c) by up to 1.3%, decreasing fasting and postprandial glucose concentrations, reducing weight by approximately 3.0 kg, and improving cardiovascular risk factors. The second class, the dipeptidyl peptidase-4 inhibitors (such as sitagliptin and vildagliptin) rely on production of endogenous GLP-1 and act by reducing its turnover. The dipeptidyl peptidase-4 (DPP-4) inhibitors produce modest reductions in HbA1c (< 1%) compared with GLP-1 agonists and are generally weight-neutral. Neither GLP-1 agonists nor DPP-4 inhibitors cause hypoglycemia unless used with other agents known to increase risk.


CONCLUSIONS
GLP-1 agonists and DPP-4 inhibitors provide a valuable new treatment option for patients with type 2 diabetes and may be associated with a wider range of therapeutic benefits than older drugs.
Pratley
Richard E
RE
Department of Medicine, Diabetes and Metabolism Translational Medicine Unit, Division of Endocrinology, Diabetes and Metabolism, University of Vermont College of Medicine, Burlington, USA. richard.pratley@uvm.edu