Saxagliptin: a review of its use as combination therapy in the management of type 2 diabetes mellitus in the EU.

Saxagliptin (Onglyza™) is a dipeptidyl peptidase 4 inhibitor widely approved for the treatment of type 2 diabetes mellitus. In the EU, saxagliptin is indicated as combination therapy with metformin, a sulfonylurea, a thiazolidinedione, or insulin (with or without metformin) for the treatment of adult patients with type 2 diabetes, including those with mild to severe renal impairment. This article reviews the clinical efficacy and tolerability of add-on saxagliptin therapy in patients with type 2 diabetes, in line with its approved indications in the EU, and summarizes the drug's pharmacological properties. The clinical efficacy of saxagliptin 5 mg/day in combination with metformin, glibenclamide (glyburide), a thiazolidinedione, or insulin (with or without metformin) has been demonstrated in several randomized, double-blind, placebo-controlled, multicentre, phase III trials (18-104 weeks in duration) in patients with type 2 diabetes. In these trials, glycosylated haemoglobin (HbA(1c)) was changed from baseline (primary endpoint) by a greater extent with add-on saxagliptin 5 mg/day (-1.09% to +0.03%) than with comparator regimens (-0.44% to +0.69%). Two other randomized, double-blind trials showed that saxagliptin 5 mg/day as add-on therapy to metformin was noninferior to uptitrated glipizide in terms of lowering HbA(1c) (-0.74% vs -0.80%) at 52 weeks, or sitagliptin (-0.52% vs -0.62%) at 18 weeks. Saxagliptin 2.5 mg/day as add-on to existing anti-diabetic therapy was also effective for up to 52 weeks in a randomized, double-blind, placebo-controlled, multicentre trial in patients with type 2 diabetes and renal impairment (HbA(1c) was reduced by 1.08% vs 0.36%; p ≤ 0.007). Saxagliptin as add-on therapy for up to 4 years was generally well tolerated in clinical trials. Treatment with saxagliptin did not increase the risk of hypoglycaemia or cardiovascular outcomes relative to placebo or active comparators, and was generally weight neutral. In conclusion, saxagliptin is a useful option as add-on therapy to metformin, a sulfonylurea, a thiazolidinedione, or insulin (with or without metformin) in patients with type 2 diabetes who require combination therapy.