Objective: To review the pharmacology, pharmacokinetics, and clinical efficacy and safety of linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor recently approved in the US for use as a treatment for type 2 diabetes mellitus.
Data sources: English-language articles in the PubMed database to October 2011 (selected using the search terms linagliptin, alogliptin, sitagliptin, saxagliptin, vildagliptin, and pharmacokinetics, pharmacodynamics, or diabetes) were identified for review. Reference lists from identified articles were reviewed for additional references of interest. Abstracts published at relevant meetings were also evaluated, and information was obtained from the manufacturer.
Study selection and data extraction: Publications reporting the pharmacology, pharmacokinetics, and clinical efficacy and safety of linagliptin were reviewed.
Data synthesis: Linagliptin therapy results in clinically meaningful reductions in hemoglobin A(1c), as well as fasting and postprandial plasma glucose levels in patients with type 2 diabetes mellitus. It contrasts with other agents in its class by not requiring dosage adjustment in patients with renal or hepatic impairment. Oral doses of linagliptin 5 mg once daily have been shown to be clinically effective, well tolerated, and weight-neutral. An increased rate of hypoglycemia when linagliptin was used in combination with an insulin secretagogue compared to placebo was noted in clinical trials.
Conclusions: Linagliptin provides an additional therapeutic option for type 2 diabetes mellitus and, in contrast to other agents in the DPP-4 class, can be used without dose adjustment in patients with any degree of declining renal function.