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

被引:365
作者
DeFronzo, Ralph A. [1 ]
Hissa, Miguel N. [2 ]
Garber, Alan J. [3 ]
Gross, Jorge Luiz [4 ]
Duan, Raina Yuyan [5 ]
Ravichandran, Shoba [5 ]
Chen, Roland S. [5 ]
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA
[2] Hosp Univ Walter Cantidio, Fortaleza, Ceara, Brazil
[3] Baylor Coll Med, Houston, TX 77030 USA
[4] Ctr Pesquisa Diabet, Porto Alegre, RS, Brazil
[5] Bristol Myers Squibb Co, Princeton, NJ USA
关键词
GLUCAGON-LIKE PEPTIDE-1; ORAL GLUCOSE-TOLERANCE; GLYCEMIC DURABILITY; INSULIN-RESISTANCE; INHIBITOR; MONOTHERAPY; SECRETION; MELLITUS; POTENT;
D O I
10.2337/dc08-1984
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 with metformin alone. RESEARCH DESIGN AND METHODS - This was a randomized, double-blind, placebo-controlled study of saxagliptin (2.5, 5, or 10 mg once daily) or placebo plus a stable dose of metformin (1,500-2,500 mg) in 743 patients (A1C; 7.0 and <= 10.0%). Efficacy analyses were performed using an ANCOVA model using last observation carried forward methodology on primary (A1C) and secondary (fasting plasma glucose [FPG] and postprandial glucose [PPG] area under the curve [AUC]) end points. RESULTS - Saxagliptin (2.5, 5, and 10 mg) plus metformin demonstrated statistically significant adjusted mean decreases from baseline to week 24 versus placebo in A1C (-0.59, -0.69, and -0.58 vs. +0.13%; all P < 0.0001), FPG (-14.31, -22.03, and -20.50vs. +1.24 mg/dl; all P < 0.0001), and PPG AUC (-8,891, -9,586, and -8,137 vs. -3,291 mg . min/dl; all P < 0.0001). More than twice as many patients achieved A1C <7.0% with 2.5, 5, and 10 mg saxagliptin versus placebo (37, 44, and 44 vs. 17%; all P < 0.0001). R-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 those with placebo. CONCLUSIONS - Saxagliptin once daily added to metformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indexes versus placebo added to metformin in patients with type 2 diabetes inadequately controlled With metformin alone.
引用
收藏
页码:1649 / 1655
页数:7
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