Sitagliptin and metformin combination therapy for the treatment of Type 2 diabetes

Insulin secretion and insulin sensitivity are impaired in Type 2 diabetes. Metformin improves insulin sensitivity by inhibiting hepatic glucose release. It is the preferred drug for first-line treatment in Type 2 diabetes. Sitagliptin, the first marketed dipeptidyl peptidase-IV inhibitor, improves insulin and glucagon secretions of the pancreatic beta- and alpha-cells, respectively, in a strictly glucose-dependent manner by raising endogenous active glucagon-like peptide-1 concentrations. The combination of metformin and sitagliptin thus offers a beneficial and complementary addition of important drug actions on insulin resistance and insulin secretion. Metformin and sitagliptin are also available as a fixed-dose combination. This article reviews the published clinical studies on both substances and their combination, and evaluates the potential benefit of the metformin plus sitagliptin combination.