This is a 24-week randomized, double-blind, placebo-controlled study of patients with type 2 diabetes and inadequate glycemic control on a stable dose of metformin. Subjects were randomized to receive saxagliptin 2.5, 5, or 10 mg, or placebo in addition to their stable dose of metformin at entry in to the trial. The primary efficacy outcome was change in A1c. Secondary endpoints included change in FPG, the percentage of patients at A1c below 7%, 2-hour postprandial glucose during OGTT, and change in fasting and postprandial glucagon, insulin, and C-peptide. The study population had a mean age of 54.6 years, mean duration of diabetes of 6.5 years,, baseline A1c of 8.0% with baseline FPG of 176 mg/dl. Daily metformin dose at entry ranged from 500-2550 mg. Treatment with saxagliptin led to clinically and statistically significant reductions in A1c from baseline vs. metformin plus placebo. Differences in adjusted mean change from baseline vs. placebo ranged from –0.73 to –0.83%. Maximal A1c reductions were reached at 12 weeks and sustained through the 24 weeks of the study. The percentage of patients achieving an A1c <7.0% was comparable for saxagliptin 5- and 10-mg. A greater percentage of saxagliptin patients achieved an A1c <7.0% vs metformin plus placebo. The overall frequency of confirmed hypoglycemia was similar between the two groups (0.5% vs 0.6%). These data confirm that there is additional A1c lowering when saxagliptin is added to ongoing metformin therapy. The data suggests that there is not benefit to exceed 5 mg once daily. It does show that there is still efficacy after 6.5 years of known diabetes. Thus saxagliptin is another tool to add to our armamentarium as we try to safely get A1cs to goal while minimizing side effects. Kittie Wyne, MD, PhD, FACE