The placement of DPP-4 inhibitors in clinical practice recommendations for the treatment of type 2 diabetes.

OBJECTIVE

To review the most recent clinical data on the safety and efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors and to evaluate their position in current treatment guidelines and algorithms.

METHODS

PubMed searches were performed to identify published data regarding both the safety and efficacy of DPP-4 inhibitors approved for use in the United States and clinical guidelines describing recommendations for their use.

RESULTS

In the past 2 years, more than 100 publications have added clinical trial data on DPP-4 inhibitors to the medical literature. Since becoming available in 2006, these agents have demonstrated an excellent safety/tolerability profile, and as add-on to metformin, DPP-4 inhibitors may have comparable glycemic efficacy as other oral agents. As a result, DPP-4 inhibitors have assumed roles in clinical practice guidelines and treatment algorithms that are comparable to the sulfonylurea class. Advantages of DPP-4 inhibitors include an oral route of administration, a mechanism of action based on glucose-stimulated insulin secretion, and a low risk of hypoglycemia. The main disadvantage associated with this class is a relatively high cost. There is also less clinical experience with DPP-4 agents than classes of agents that have been in use for decades; however, long-term data on the safety and efficacy of DPP-4 agents will be available in the near future to refine their place in therapy. From 2 large clinical trials recently reported, EXAMINE and SAVOR, this class of agents does not increase overall adverse cardiovascular outcomes nor the risk of pancreatitis or pancreatic cancer.

CONCLUSION

Based on comparisons of nonglycemic effects such as risk of hypoglycemia, weight gain, and durability, DPP-4 inhibitors may be considered as an alternative to sulfonylureas. However, direct cost may be a determining factor in the choice of therapy.