Linagliptin: DPP-4 Inhibition in the Treatment of Type 2 Diabetes Mellitus

The complex pathophysiologic mechanisms of type 2 diabetes are one of the barriers that make its treatment so difficult and it is also one of the responsible for the high prevalence of the disease around the world. Patients with T2DM have dysfunction in incretin hormones (such as glucagon-like peptide-1 or GLP-1 and glucose-dependent insulinotropic polypeptide or GIP). By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level decrease in a glucose-dependent manner. Linagliptin is a dipeptidyl peptidase-4 inhibitor. This article reviews the pharmacology, mechanism of action, chemical structure, enzymatic binding, pharmacokinetics, pharmacodynamics, clinical trials, indications, contraindications and drug interactions of linagliptin and the role of DPP-4 inhibitors in the management of hyperglycemia in adults with T2DM. Linagliptin clinical trials showed clinical efficacy in decreasing glycated hemoglobin (HbA1c), fasting plasma glucose and postprandial glucose when administered as monotherapy or in combination with other oral antihyperglycemic agents (such as sulphonylureas, pioglitazone or metformin) and also insulin, including non-inferior efficacy versus sulphonylurea without weight gain. Adverse events are uncommon and may include upper respiratory tract infection, nasopharyngitis and headache. The risk of hypoglycemia with linagliptin is very low and is increased when the drug is combined with insulin or an insulin secretagogue drug, such as a sulphonylurea. Dose adjustments based on liver or renal function are not necessary with linagliptin use. Given its safety and efficacy profile, linagliptin is a valid treatment for patients with T2DM and is a particularly interesting option in patients with renal failure.