Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes.

Type 2 diabetes is a progressive disease for which current treatments are often unsatisfactory with respect to achieving therapeutic goals and unwanted side effects. Preclinical and clinical studies of linagliptin, a new oral antidiabetic agent, including data presented at Scientific Meetings and peer-reviewed studies published since 2007. This article reviews pharmacokinetic and pharmacodynamic characteristics of linagliptin. Linagliptin belongs to a new chemical class of dipeptidyl pepidase-4 (DPP-4) inhibitors, which comprise xanthine-based compounds. It is a potent, long-acting inhibitor with high selectivity for DPP-4 versus the related enzymes DPP-8 and DPP-9. The drug has modest oral availability in humans, but is absorbed rapidly to inhibit plasma DPP-4 activity by > 80% over 24 h. It is not metabolized appreciably in vivo, but binds extensively to plasma proteins, with elimination occurring primarily in the liver. Linagliptin reduces degradation of the incretin hormone glucagon-like peptide-1 and is associated with reduced fasting and postprandial glucose in preclinical and clinical studies. Limited data from longer duration clinical trials show it improves glycemic control in patients with type 2 diabetes. Linagliptin is a new oral antidiabetic agent associated with minimal risk of hypoglycemia, which holds promise for treatment of type 2 diabetes.