Linagliptin for the treatment of type 2 diabetes (pharmacokinetic evaluation).
BACKGROUND
Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). The novel compound linagliptin has important different pharmacokinetic (PK) properties, when compared with previously commercialized DPP-4 inhibitors, which may offer some advantages in clinical practice. Linagliptin has a unique PK/pharmacodynamic (PD) profile and is the first DPP-4 inhibitor with a nonrenal elimination route. Therefore, it can be administered in patients with renal impairment without dose adjustment or monitoring of renal function. The drug has a low potential for drug-drug interactions (DDIs) and no clinically relevant ones were reported so far.


METHODS
An extensive literature search was performed to analyse primarily PK and secondarily PD characteristics of linagliptin in both healthy volunteers and patients with T2DM (treated with linagliptin as monotherapy or combined therapy). Updated information about linagliptin PK either after single administration (large dose range) or after chronic administration (steady state) were also included. A special focus has been put on DDIs and on PK/PD of linagliptin in patients with renal impairment.


CONCLUSIONS
Head-to-head comparative studies and/or increased clinical experience with DPP-4 inhibitors will determine the clinical advantage, if any, of one agent over another.
University of Liège, Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine, CHU Sart Tilman (B35), B-4000 Liege 1, Belgium. andre.scheen@chu.ulg.ac.be
André J
AJ
Scheen
D019540:Area Under Curve; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D005905:Glyburide / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069476:Linagliptin; D008687:Metformin / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077205:Pioglitazone; D011687:Purines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011799:Quinazolines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051297:Sodium-Glucose Transporter 2 / Q000627:therapeutic use; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D045162:Thiazolidinediones / Q000493:pharmacokinetics / Q000627:therapeutic use
D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D011687:Purines; D011799:Quinazolines; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D045162:Thiazolidinediones; D000069476:Linagliptin; D008687:Metformin; D005905:Glyburide; D000077205:Pioglitazone