Linagliptin: A Novel Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor forTreatment of Type II Diabetes Mellitus

Abstract

Type 2 diabetes mellitus causes significant morbidity and mortality on account of its progressive nature and results in considerable burden on healthcare resources. Current treatment strategies have only limited long-term efficacy and tolerability given the progressive nature of the disease leading to inadequate glycemic control and are also associated with undesirable side effects such as weight gain, hypoglycemia and gastrointestinal distress. In the light of these existing limitations, exploring new treatment targets and new therapies have become the need of the hour at present. The incretin pathway, in particular, glucagon-like peptide (GLP-1), plays an important pathological role in the development of type 2 diabetes mellitus, and treatments targeting the incretin system have recently generated surmount interest. These can mainly be categorized into two broad classes; GLP-1 agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase- 4 inhibitors (sitagliptin, vildagliptin). The gliptins act by prolonging the action of incretins, the gut hormones which can boost insulin levels. Linagliptin is the latest dipeptidyl peptidase-4 inhibitor to complete pivotal phase III trials, which have demonstrated its superiority to its competitors based on its low therapeutic dose, long-lasting inhibition of DPP-4 activity and a good safety/tolerability profile. One of the unique characteristics of linagliptin is its primarily non-renal route of excretion. The drug has recently been approved by the US Food and Drug Administration and has been portrayed as a promising treatment option for patients in whom metformin and the other DPP-4 inhibitors are either contraindicated or require dose adjustment because of moderate to severe renal impairment.