Pharmacokinetic and pharmacodynamic evaluation of sitagliptin plus metformin.
BACKGROUND
Type 2 diabetes is an increasingly prevalent disease resulting from various complex combinations of defects in insulin secretion and insulin action. Adequate blood glucose control is necessary to minimize complications. DPP IV inhibitors (sitagliptin, vildagliptin, saxagliptin) offer new options for combined pharmacological therapy.


METHODS
An extensive literature search was performed to analyze the potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between metformin (first-line drug for the management of type 2 diabetes) and sitagliptin (first commercialized DPP IV inhibitor). Metformin and sitagliptin may be administered together, either separately or in fixed-dose combination.


RESULTS
Updated information about PK/PD data on metformin alone, sitagliptin alone and sitagliptin plus metformin. Metformin and sitagliptin are not prone to PK drug-drug interactions. Their co-administration, either separately or in a fixed-dose combination, improves blood glucose control more potently than either compound separately, without hypoglycemia and without increasing metformin-related gastrointestinal side effects.


CONCLUSIONS
The combination sitagliptin plus metformin may be used as a first- or second-line therapy in the management of type 2 diabetes.
Scheen
André J
AJ
University of Liège, CHU Sart Tilman, Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine, Liège, Belgium . andre.scheen@chu.ulg.ac.be
D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008687:Metformin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011719:Pyrazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D011719:Pyrazines; D014230:Triazoles; D008687:Metformin; D000068900:Sitagliptin Phosphate