Small molecule dipeptidylpeptidase IV inhibitors under investigation for diabetes mellitus therapy.

INTRODUCTION: A recent treatment advance for type 2 diabetes is the oral therapy with DPP IV inhibitors. New substances of this class are in development in order to increase alternatives for treating this important metabolic disease. The reader will gain detailed pharmacological and clinical information on alogliptin, dutogliptin and linagliptin and will learn how these DPP IV inhibitors may widen the whole drug class. Possible special indications for the various DPP IV inhibitors are discussed. AREAS COVERED: The DPP IV inhibitors and their current role in type 2 diabetes are highlighted. Preclinical and clinical studies of the novel DPP IV inhibitors alogliptin, dutogliptin and linagliptin, including published data since 2007, are presented and a comparison of these compounds is made. EXPERT OPINION: The efficacy and safety profile of DPP IV inhibitors are promising and advantageous so far. In contrast to sulfonylureas, DPP IV inhibitors do not have an intrinsic risk for causing hypoglycemia and they are body weight neutral. Their tolerability profile is good and no specific adverse reactions have been reported. Experience so far suggests that there are no safety issues associated with inhibition of DPP IV activity by itself. Novel DPP IV inhibitors with distinct properties may offer alternative choices within this drug class.