The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes on Metformin Alone

Abstract

Objective: This 24-week trial assessed the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes with inadequate glycemic control on metformin alone.

Research design and methods: Randomized, double-blind, placebo-controlled study of saxagliptin (2.5, 5, 10 mg once daily) or placebo plus stable dose of metformin (1500–2500 mg) in 743 patients (A1C ≥7.0% and ≤10.0%). Efficacy analyses were performed using an ANCOVA model utilizing last-observation-carried-forward methodology on primary (A1C) and secondary (FPG, PPG-AUC) endpoints.

Results: Saxagliptin 2.5, 5, and 10 mg plus metformin demonstrated statistically significant adjusted mean decreases from baseline to week 24 vs. placebo in A1C (−0.59%, −0.69%, −0.58% vs. + 0.13%, all P< 0.0001) FPG (−14.31, −22.03, −20.50 mg/dl vs. +1.24 mg/dl, all P< 0.0001) and PPG-AUC (−8891, −9586, −8137 mg•min/dl vs. −3291 mg•min/dl, all P< 0.0001). More than twice as many patients achieved A1C <7.0% with saxagliptin 2.5, 5, and 10 mg vs. placebo (37%, 44%, 44% vs. 17%, all P< 0.0001). β-Cell function and postprandial C-peptide, insulin, and glucagon AUCs improved in all saxagliptin treatment groups at week 24. Incidence of hypoglycemic adverse events and weight reductions were similar to placebo.

Conclusions: Saxagliptin once daily added to metformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indices vs. placebo added to metformin in patients with type 2 diabetes inadequately controlled on metformin alone.