Efficacy of saxagliptin as an add-on to oral monotherapy in the phase 3 clinical development program: predictive factors of the treatment response in type 2 diabetes.

Saxagliptin, a dipeptidyl peptidase-4 inhibitor, has been the focus of a large clinical development programme, including Phase 3 randomized vs placebo-controlled clinical trials as add-on therapy in patients with type 2 diabetes (T2D) with inadequate glycemic control using initial monotherapy (metformin, glibenclamide, thiazolidinedione). This clinical programme has shown saxagliptin to be effective in the control of fasting and postprandial glycemic parameters, in addition to a good overall safety profile. The present paper aims at reviewing the overall short-term and long-term efficacy of saxagliptin in its Phase 3 development program and tries to pinpoint some factors that may be more predictive of treatment response in clinical practice. In individual and pooled analyses of the three pivotal add-on to monotherapy trials, saxagliptin (5mg once daily) led to significant reductions in HbA(1c) from baseline to 24 weeks. Additional analyses showed that reductions in HbA(1c) were maintained in the long-term, notably for 102 weeks, in combination with metformin. Data have also shown that the absolute reduction in HbA(1c) seen with saxagliptine from baseline to Week 24 was numerically greater with an elevated baseline HbA(1c). In these recently published pooled analyses, clinically pertinent reductions in HbA(1c) were also obtained with saxagliptin across a wide range of subgroups of T2D patients when examined either by specific baseline demographic characteristics or by β-cell function indices such as the HOMA-β.