Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin

BACKGROUND In four 24-week controlled studies, the antihyperglycaemic efficacy of saxagliptin was demonstrated in patients with type 2 diabetes mellitus as add-on therapy to glyburide, a thiazolidinedione, or metformin, and when used in initial combination with metformin vs. metformin monotherapy in drug-naive patients. METHODS Data from these studies were analysed to compare the proportions of patients who achieved specific reductions from baseline in glycated haemoglobin [HbA(1c); reductions of ≥ 0.5% and ≥ 0.7% in all studies (prespecified); reductions ≥ 1.0% in the add-on studies and ≥ 1.0% to ≥ 2.5% in the initial combination study (post hoc)] for saxagliptin vs. comparator at week 24. We report overall rates of glycaemic response defined by these reductions in HbA(1c) and rates of response without experiencing hypoglycaemia. RESULTS Large glycaemic response rates were higher with saxagliptin 2.5 and 5 mg/day than with comparator (HbA(1c) ≥ 1.0%, 31.7-50.3% vs. 10.3-20.0%) as add-on therapy and higher with saxagliptin 5 mg/day as initial combination with metformin than with metformin monotherapy (HbA(1c) ≥ 2.0%, 68.3% vs. 49.8%) in drug-naive patients. Addition of saxagliptin was associated with a low incidence of hypoglycaemia; overall response rates and response rates excluding patients who experienced hypoglycaemia were similar. Analysis of several demographic and baseline clinical variables revealed no consistent correlations with response to saxagliptin. CONCLUSIONS Whether receiving saxagliptin as an add-on therapy to glyburide, a thiazolidinedione, or metformin or in initial combination with metformin, a greater percentage of patients achieve clinically relevant large reductions in HbA(1c) vs. comparator, with a low incidence of hypoglycaemia.