Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial

被引:193
作者
Chacra, A. R. [1 ]
Tan, G. H. [2 ]
Apanovitch, A. [3 ]
Ravichandran, S. [3 ]
List, J. [3 ]
Chen, R. [3 ]
机构
[1] Univ Fed Sao Paulo, Ctr Diabet, Sao Paulo, Brazil
[2] Cebu Doctors Univ Hosp, Cebu Doctors Univ Coll Med, Cebu, Philippines
[3] Bristol Myers Squibb Co, Princeton, NJ USA
关键词
EUROPEAN-ASSOCIATION; INSULIN SENSITIVITY; CONSENSUS STATEMENT; THERAPY; METFORMIN; ROSIGLITAZONE; MANAGEMENT; HYPERGLYCEMIA; COMBINATION; ADJUSTMENT;
D O I
10.1111/j.1742-1241.2009.02143.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims: Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy. Methods and patients: A total of 768 patients (18-77 years; HbA(1c) screening >= 7.5 to < 10.0%) were randomised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks. Blinded uptitration glyburide was allowed in the glyburide-only arm to a maximum total daily dose of 15 mg. Efficacy analyses were performed using ANCOVA and last-observation-carried-forward methodology. Results: At week 24, 92% of glyburide-only patients were uptitrated to a total glyburide dose of 15 mg/day. Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide, respectively, in HbA(1c) (-0.54%, -0.64% vs. +0.08%; both p < 0.0001) and fasting plasma glucose (-7, -10 vs. +1 mg/dl; p = 0.0218 and p = 0.002). The proportion of patients achieving an HbA(1c) < 7% was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (22.4% and 22.8% vs. 9.1%; both p < 0.0001). Postprandial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (-4296 and -5000 vs. +1196 mg center dot min/dl; both p < 0.0001). Adverse event occurrence was similar across all groups. Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 (13.3%) and 5 mg (14.6%) vs. uptitrated glyburide (10.1%). Conclusion: Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated.
引用
收藏
页码:1395 / 1406
页数:12
相关论文
共 31 条
[1]   Standards of medical care in diabetes 2008 [J].
不详 .
DIABETES CARE, 2008, 31 :S12-S54
[2]   Efficacy and safety of incretin therapy in type 2 diabetes - Systematic review and meta-analysis [J].
Amori, Renee E. ;
Lau, Joseph ;
Pittas, Anastassios G. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 298 (02) :194-206
[3]   Association between oral antidiabetic use, adverse events and outcomes in patients with type 2 diabetes [J].
Asche, C. V. ;
McAdam-Marx, C. ;
Shane-McWhorter, L. ;
Sheng, X. ;
Plauschinat, C. A. .
DIABETES OBESITY & METABOLISM, 2008, 10 (08) :638-645
[4]   Discovery and preclinical profile of saxagliptin (BMS-477118): A highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes [J].
Augeri, DJ ;
Robl, JA ;
Betebenner, DA ;
Magnin, DR ;
Khanna, A ;
Robertson, JG ;
Wang, AY ;
Simpkins, LM ;
Taunk, P ;
Huang, Q ;
Han, SP ;
Abboa-Offei, B ;
Cap, M ;
Xin, L ;
Tao, L ;
Tozzo, E ;
Welzel, GE ;
Egan, DM ;
Marcinkeviciene, J ;
Chang, SY ;
Biller, SA ;
Kirby, MS ;
Parker, RA ;
Hamann, LG .
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (15) :5025-5037
[5]   Earlier intervention in type 2 diabetes: The case for achieving early and sustained glycaemic control [J].
Bailey, CJ ;
Del Prato, S ;
Eddy, D ;
Zinman, B .
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, 2005, 59 (11) :1309-1316
[6]   Comparison of uptitration of gliclazide with the addition of rosiglitazone to gliclazide in patients with type 2 diabetes inadequately controlled on half-maximal doses of a sulphonylurea [J].
Baksi, A ;
James, RE ;
Zhou, B ;
Nolan, JJ .
ACTA DIABETOLOGICA, 2004, 41 (02) :63-69
[7]   DPP-4 inhibitors and their potential role in the management of type 2 diabetes [J].
Barnett, A. .
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, 2006, 60 (11) :1454-1470
[8]   The burden of treatment failure in type 2 diabetes [J].
Brown, JB ;
Nichols, GA ;
Perry, A .
DIABETES CARE, 2004, 27 (07) :1535-1540
[9]   β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes [J].
Butler, AE ;
Janson, J ;
Bonner-Weir, S ;
Ritzel, R ;
Rizza, RA ;
Butler, PC .
DIABETES, 2003, 52 (01) :102-110
[10]   Mechanisms of β-cell death in type 2 diabetes [J].
Donath, MY ;
Ehses, JA ;
Maedler, K ;
Schumann, DM ;
Ellingsgaard, H ;
Eppler, E ;
Reinecke, M .
DIABETES, 2005, 54 :S108-S113