Pharmacokinetic and pharmacodynamic evaluation of sitagliptin plus metformin.

IMPORTANCE OF THE FIELD: 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. AREAS COVERED IN THIS REVIEW: 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. WHAT THE READER WILL GAIN: 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. TAKE HOME MESSAGE: The combination sitagliptin plus metformin may be used as a first- or second-line therapy in the management of type 2 diabetes.