Review of linagliptin for the treatment of type 2 diabetes mellitus.

Background: Linagliptin is a dipeptidyl peptidase-4 inhibitor that was approved in 2011 by the US Food and Drug Administration as a treatment adjunctive to diet and exercise for the improvement of glycemic control in adults with type 2 diabetes mellitus (T2DM).

Objective: The purpose of this article is to review the pharmacology, pharmacokinetic properties, efficacy, tolerability including drug-drug interactions, contraindications/precautions, and dosage and administration of linagliptin, and the potential role of linagliptin in the management of glycemia in adults with T2DM.

Methods: MEDLINE (1966-January 12, 2012), PubMed (1950-January 12, 2012), Science Direct (1994-January 12, 2012), Web of Science (1980-January 12, 2012), and the American Diabetes Association Scientific Abstracts (2008-2011) were searched using the term linagliptin. Articles and abstracts published in English, both original research and review articles, were identified for review. Reference lists from identified articles were also searched for additional references of interest. Manufacturers' prescribing information was additionally examined.

Results: Data from clinical trials of linagliptin suggest clinical efficacy in terms of reductions in hemoglobin A(1c) (A(1c)), fasting plasma glucose, and postprandial glucose when linagliptin was administered as monotherapy or in combination with other oral antidiabetic agents, with placebo-subtracted A(1c) changes ranging from -0.47% to -0.69% in placebo-controlled trials. Adverse events that occurred in ≥2% of patients treated with linagliptin and at a prevalence of ≥2-fold greater compared with placebo were nasopharyngitis, hyperlipidemia, cough, hypertriglyceridemia, and weight increase (when used in combination with a thiazolidinedione [TZD]). Although linagliptin administered as monotherapy or in combination with metformin or a TZD may convey a low risk for hypoglycemia (0%-1.2%), caution is warranted when linagliptin is administered in combination with insulin secretagogues due to an increased risk for hypoglycemic events. Dosage adjustments based on renal or hepatic function are not required. Additionally, according to the currently approved prescribing information, the efficacy of linagliptin may be limited in patients receiving concurrent inducers of the cytochrome P450 3A4 isozyme or P-glycoprotein (eg, rifampin).

Conclusions: Based on the findings from the present review, patients and clinicians should be aware of the risk for hypoglycemia when linagliptin is prescribed as a treatment adjunctive to a regimen of an insulin secretagogue. An initial dose decrease in the secretagogue should be considered to prevent hypoglycemic events. Dosage adjustment of linagliptin is not required in patients with renal impairment.