title: Linagliptin plus metformin: a pharmacokinetic and pharmacodynamic evaluation.
abstract: BACKGROUND
  The first-choice drug therapy in the management of type 2 diabetes is metformin . However, most patients require a combined therapy to reach and/or maintain targets of glucose control. Dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly referred to as gliptins, offer new options for combined therapy with metformin. Linagliptin is the most recently launched gliptin, with a unique pharmacokinetic (PK) profile characterized by negligible renal excretion and is now also available as a fixed-dose combination (FDC) with metformin.
  
  
  METHODS
  An extensive literature search was performed to analyze the potential PK and pharmacodynamic interactions between linagliptin and metformin. Linagliptin and metformin may be administered together, either separately or as FDC supported by bioequivalence studies. Linagliptin and metformin are not prone to PK drug-drug interactions. Their coadministration improves blood glucose control more potently than either compound separately, without hypoglycemia and without increasing metformin-related gastrointestinal side effects.
  
  
  CONCLUSIONS
  The combination linaglitpin plus metformin, if not contraindicated (renal failure), may be used as first-line or second-line therapy in the management of type 2 diabetes. That being said, the durability of the glucose-lowering effect of this combination needs to be further explored in long-term controlled trials.
authors: University of Liège, Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Sart Tilman, B-4000 Liege 1, Belgium. andre.scheen@chu.ulg.ac.be
authors: André J
authors: AJ
authors: Scheen
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004347:Drug Interactions; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069476:Linagliptin; D008687:Metformin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011687:Purines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011799:Quinazolines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011687:Purines; D011799:Quinazolines; D000069476:Linagliptin; D008687:Metformin