Abstract
Patients with type 2 diabetes mellitus (T2DM) frequently require multiple therapies to effectively control hyperglycemia, and many new agents for glucose control have been developed over the past few decades. Linagliptin is a recently approved oral antidiabetic drug that acts by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4). Unlike other DPP-4 inhibitors, linagliptin is excreted chiefly via the enterohepatic system, and can be used without dose adjustment in patients with renal or hepatic impairment. Linagliptin was approved by the US Food and Drug Administration based on a large development program, including four pivotal trials in patients with T2DM, assessing the efficacy and safety of linagliptin when used as monotherapy or in combination with other oral antidiabetes drugs. Linagliptin was associated with significant improvements in glycosylated hemoglobin, fasting plasma glucose and postprandial glucose, and more patients receiving linagliptin showed meaningful improvements and achieved targets for glycosylated hemoglobin. Linagliptin was well tolerated, with an adverse event profile similar to that of placebo, and low rates of hypoglycemic events. Taken together, the pivotal trials confirm linagliptin is effective and safe in patients with T2DM: the convenience of oral dosing with no requirement for dose adjustment in patients with renal or hepatic impairment make linagliptin a valuable option when considering therapies for patients with T2DM.