This paper reports a 24 week, phase 3, multicenter randomized, double-blind, active-controlled international trial evaluating combination therapy with saxagliptin/metformin vs. saxagliptin or metformin monotherapy in treatment-naïve T2DM. They found that combination therapy resulted in statistically significant reductions in A1c, fasting and postprandial glucose, compared with either monotherapy group. 60% of the people treated with combination therapy attained an A1c <7% compared to 32 & 41% with saxagliptin or metformin, respectively. The high percent getting to goal with the combination is likely related to the fact that mean baseline A1cs were above 9% with an average duration of diabetes </= 2 years and most were truly treatment naïve, as opposed to having been on meds that were stopped to get them in to the study As has consistently been seen in glucose lowering studies, the largest decreases in A1c occurred in those with the highest baselines. The subgroup that received combination therapy who started with an A1c =10% had a decrease in A1c of 3.3%, regardless of dose of saxagliptin. Statistically significant improvements in ß-cell function, based on HOMA modeling, occurred, with little or no effect on postprandial glucagon AUC at week 24 in all treatment groups. Modest amounts of weight loss occurred in all groups (ie 1.1-1.8 kg). Numerical improvements in lipid parameters occurred in all groups. Overall, the saxagliptin was well tolerated with few side effects and a low incidence of hypoglycemia. The clinical utility of this Phase 3 trial is up to the reader to discern. It certainly adds to the body of data showing that early combination therapy can be more effective than monotherapy. It would have been nice to be able to continue these assignments for at least 2-5 years to assess the durability of this combination. Kittie Wyne, MD, PhD, FACE