Inhibition of DPP-4 is emerging as a viable therapeutic option for patients with type 2 diabetes. The incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, act to augment insulin secretion and are released during postprandial nutrient absorption in the gastrointestinal tract. Incretin activity is extended via suppression of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide degradation with DPP-4 inhibitors.
20 As monotherapy, DPP-4 inhibitors (ie, alogliptin, saxagliptin, sitagliptin, vildagliptin) demonstrate approximately 0.5% to 1.0% reduction in HbA
1c levels, and durability of that effect has been demonstrated with saxagliptin, sitagliptin, and vilda gliptin.
13,21-23 Treatment-naïve patients with type 2 diabetes (mean baseline HbA
1c level of 8.4%) treated with vildagliptin (100 mg/d) for up to 2 years demonstrated a mean (standard deviation) reduction in HbA
1c levels of 1.0% (0.1%).
21 After completion of a double-blind, 54-week study to examine the long-term efficacy and safety of sitagliptin given in combination with metformin as initial therapy in patients with type 2 diabetes, 402 patients entered a 50-week extension of the study.
22 After 104 weeks (2 years) of treatment, monotherapy with sitagliptin and initial combination therapy with sitagliptin plus metformin were shown to provide substantial and long-term improvements in glycemic control (mean change in HbA
1c level, –1.2% to –1.7%).
22 Similarly, in patients whose type 2 diabetes was inadequately controlled with metformin alone, saxagliptin (2.5, 5, or 10 mg) added to metformin provided sustained, clinically meaningful glycemic improvements compared with placebo during 102 weeks; the difference in HbA
1c levels between study patients and control patients was –0.52% to –0.72%.
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