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.