Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin

摘要

Objective: To evaluate efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes (T2D) with inadequate glycemic control on insulin alone or combined with metformin. Methods: Adults (n=455) with HbA 1c 7.511% on stable insulin therapy (30150U/day±metformin) for at least 8 weeks were stratified by metformin use and randomly assigned 2:1 to receive saxagliptin 5mg or placebo once daily for 24 weeks. Patients were to maintain stable insulin doses but these could be decreased to reduce risk of hypoglycemia. Patients with hyperglycemia or substantially increased insulin use were rescued with a flexible insulin regimen and remained in the study. Metformin doses were kept stable. The primary efficacy endpoint was change in HbA 1c from baseline to week 24 (or rescue). Results: Patients treated with saxagliptin versus placebo had significantly greater reductions in adjusted mean HbA 1c (difference:-0.41%, p0.0001), postprandial glucose (PPG) 180-minute area under the curve (-3829.8 mg?min/dL, p=0.0011), and 120-minute PPG (-23.0 mg/dL, p=0.0016) at 24 weeks. Treatment with saxagliptin resulted in similar reductions in HBA 1c relative to placebo, irrespective of metformin treatment. At 24 weeks, difference in adjusted mean fasting plasma glucose for saxagliptin versus placebo was-4.02mg/dL (p=0.3958); 17.3% and 6.7% of patients in the saxagliptin and placebo groups, respectively, achieved HbA 1c7%. Mean change from baseline in body weight at week 24 was 0.39kg for saxagliptin and 0.18kg for placebo. Hypoglycemia was reported in 18.4% and 19.9% of patients in the saxagliptin and placebo groups, respectively (confirmed hypoglycemia: 5.3%, 3.3%). Other adverse events reported in at least 5% of patients were urinary tract infection (saxagliptin, placebo: 5.9%, 6.0%), influenza (3.0%, 6.6%), and pain in extremity (1.6%, 6.0%). Conclusions: Saxagliptin 5-mg once-daily add-on therapy improves glycemic control in T2D patients on insulin alone or combined with metformin and is generally well-tolerated.