A Randomized Clinical Trial to Evaluate the Efficacy and Safety of Co-Administration of Sitagliptin with Intensively Titrated Insulin Glargine

作者：Mathieu Chantal; Shankar R Ravi^*; Lorber Daniel; Umpierrez Guillermo; Wu Fan; Xu Lei; Golm Gregory T; Latham Melanie; Kaufman Keith D; Engel Samuel S

来源：Diabetes Therapy, 2015, 6(2): 127-142.

DOI：10.1007/s13300-015-0105-3

• DPP-4 inhibitors
• Incretin therapy
• Insulin glargine
• Insulin sparing
• Sitagliptin
• Type 2 diabetes mellitus

Introduction: The objective of this study was to assess the effect of sitagliptin on insulin dose in patients with inadequately controlled type 2 diabetes who titrate basal insulin to a target fasting glucose level after initiating sitagliptin.
Methods: This was a multicenter, randomized, double-blind, placebo-controlled, 24-week clinical trial in which treatment with sitagliptin 100 mg/day or placebo was administered concurrently with insulin glargine titration, targeting a fasting glucose of 4.0-5.6 mmol/L (72-100 mg/dL). The trial randomized 660 patients with type 2 diabetes and inadequate glycemic control on insulin, with or without metformin (>= 1500 mg/day) or sulfonylurea, for >= 10 weeks. Patients could remain on metformin but not sulfonylurea after randomization.
Results: The increase from baseline in the daily dose of insulin was less in the sitagliptin group (N = 329) compared to placebo (N = 329) (between group difference=-4.7 IU [95% confidence interval [CI] -8.3, -1.2]; p = 0.009). Patients in the sitagliptin group had lower glycated hemoglobin (HbA1c) levels after 24 weeks (between-group difference of -0.4% [95% CI -0.6, -0.3; -4.9 mmol/mol (95% CI -6.6, -3.2)]; p<0.001), and more patients in the sitagliptin group reached the HbA1c goal of <7.0% (53 mmol/mol), with a between-group difference of 17.3% (95% CI 10.4%, 24.1%; p<0.001). Fewer patients in the sitagliptin group experienced an adverse event of hypoglycemia (between-group difference = -15.5%, p<0.001).
Conclusion: Administration of sitagliptin prior to intensive titration of basal insulin glargine reduces the insulin dose requirement while providing superior glycemic control and less hypoglycemia, compared to an insulin-only regimen.

• 出版日期2015-6