The pharmacokinetic considerations and adverse effects of DPP-4 inhibitors [corrected].

INTRODUCTION: Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a class of anti-hyperglycemic agents with proven efficacy in patients with type 2 diabetes mellitus (T2DM). AREAS COVERED: This review considers the pharmacokinetic profile, adverse effects and drug interactions of DPP-4 inhibitors. DPP-4 inhibitors have certain differences in their structure, metabolism, route of elimination and selectivity for DPP-4 over structurally related enzymes, such as DPP-8/DPP-9. They have a low potential for drug interactions, with the exception of saxagliptin that is largely metabolized by cytochrome CYP3A4/A5. Reports of pancreatitis and pancreatic cancer have raised concerns regarding the safety of DPP-4 inhibitors and are under investigation. Post-marketing surveillance has revealed less common adverse effects, especially a number of skin- and immune-related adverse effects. These issues are covered in the present review. EXPERT OPINION: DPP-4 inhibitors are useful and efficient drugs. DPP-4 inhibitors have similar mechanism of action and similar efficacy. However, DPP-4 inhibitors have certain differences in their pharmacokinetic properties that may be associated with different clinical effects and adverse event profiles. Although clinical trials indicated a favorable safety profile, post-marketing reports revealed certain safety aspects that need further investigation. Certainly, more research is needed to clarify if the differences among DPP-4 inhibitors could lead to a different clinical and safety profile.