Nesina®, in Combination with Metformin

Partnership with Takeda Pharmaceuticals

Takeda is developing a combination therapeutic using Nesina® (alogliptin) and metformin in a single tablet for the treatment of type 2 diabetes (T2D). The combination is presently in Phase III studies to test its safety and efficacy. The primary outcome measure will change from baseline HbA(1c). Takeda will also look at changes in body weight and fasting glucose levels.

For patients diagnosed with T2D, metformin is the usual first-line therapy in addition to diet control and exercise. For patients with inadequate glycemic control with metformin or those who experience serious side effects of metformin, sulfonylurea is a popular choice as a second-line oral anti-diabetic treatment. Alogliptin is a DPP-4 inhibitor that slows the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), which play a major role in regulating blood glucose levels and have the potential to improve pancreatic beta-cell function.

Metformin

Takeda has previously tested the efficacy and safety of alogliptin in a Phase II study. Alogliptin was dosed once daily at 12.5 mg and 25 mg in combination with metformin in patients whose HbA(1c) levels were inadequately controlled on metformin alone. Alogliptin at both doses produced significant (p < 0.001) decreases from baseline in HbA(1c) greater than those observed with placebo. The between-treatment differences (alogliptin vs. placebo) in fasting plasma glucose reached statistical significance (p < 0.001) as early as the first week and persisted for the duration of the study.

Overall, adverse events observed with alogliptin were not substantially different from those observed with placebo. This includes low event rates for gastrointestinal side effects and hypoglycaemic episodes.

The results indicate that alogliptin is an effective and safe treatment for T2D when added to metformin for patients not sufficiently controlled on metformin monotherapy. [1]

Reference

  1. 1. Nauck MA et al. Int J Clin Pract. 2009 Jan.;63(1): p. 46-55.