Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes.

AIM: Enhancing the physiologic actions of the endogenous incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, by inhibiting dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for their degradation, is an emerging treatment for type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the safety and efficacy of dose ranges of the DPP-4 inhibitor saxagliptin (BMS-477118) in patients with T2DM. METHODS: In a 12-week, multicentre, randomized, parallel-group, double-blind, placebo-controlled trial conducted at 152 out-patient US study centres, 338 (low-dose cohort) and 85 (high-dose cohort) drug-naive patients with T2DM and inadequate glycaemic control (baseline HbA1c > or =6.8 and < or =9.7%) were randomized. Following a 2-week washout, patients received saxagliptin 2.5, 5, 10, 20 or 40 mg once daily, or placebo, for 12 weeks (low-dose cohort). In a second cohort, patients received saxagliptin 100 mg once daily, or placebo, for 6 weeks (high-dose cohort). The main outcome measure was saxagliptin dose response assessed as change from baseline in HbA1c following double-blind treatment. RESULTS: In all treatment arms, saxagliptin significantly reduced HbA1c by 0.7-0.9% from an average baseline of 7.9% vs. placebo (0.3% reduction) in the low-dose cohort. Placebo-subtracted HbA1c reductions were 0.45-0.63% (low-dose cohort). Saxagliptin had significant placebo-subtracted reductions in fasting serum glucose (14-25 mg/dl). Postprandial glucose levels at 60 min following a standard liquid meal test were reduced by 24-41 mg/dl vs. placebo. Saxagliptin was weight neutral. Adverse events were similar across treatment groups, including placebo, with a very low incidence of confirmed hypoglycaemia in saxagliptin treatment arms. CONCLUSIONS: Saxagliptin effectively improved glycaemic control in drug-naive patients with T2DM and was generally safe, with a tolerability profile similar to placebo.