Randomized, Double-Blind, Phase 3 Trial of Triple Therapy With Dapagliflozin Add-on to Saxagliptin Plus Metformin in Type 2 Diabetes

被引:129
作者
Mathieu, Chantal [1 ]
Ranetti, Aurelian Emil [2 ]
Li, Danshi [3 ]
Ekholm, Ella [4 ]
Cook, William [5 ]
Hirshberg, Boaz [6 ]
Chen, Hungta [5 ]
Hansen, Lars [3 ]
Iqbal, Nayyar [3 ]
机构
[1] Katholieke Univ Leuven, Leuven, Belgium
[2] Carol Davila Univ Med & Pharm, Bucharest, Romania
[3] Bristol Myers Squibb Co, Princeton, NJ USA
[4] AstraZeneca, Molndal, Sweden
[5] AstraZeneca, Gaithersburg, MD USA
[6] MedImmune, Gaithersburg, MD USA
关键词
INADEQUATE GLYCEMIC CONTROL; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; CLINICAL-TRIALS; BODY-WEIGHT; EFFICACY; SAFETY; 24-WEEK; SULFONYLUREA; MELLITUS; PIOGLITAZONE;
D O I
10.2337/dc15-0779
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE To compare the efficacy and safety of treatment with dapagliflozin versus that with placebo add-on to saxagliptin plus metformin in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin treatment. RESEARCH DESIGN AND METHODS Patients receiving treatment with stable metformin (stratum A) (screening HbA(1c) level 8.0-11.5% [64-102 mmol/mol]) or stable metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor (stratum B) (HbA(1c) 7.5-10.5% [58-91 mmol/mol]) for >= 8 weeks received open-label saxagliptin 5 mg/day and metformin for 16 weeks (stratum A) or 8 weeks (stratum B) (saxagliptin replaced any DPP-4 inhibitor). Patients with inadequate glycemic control (HbA(1c) 7-10.5% [53-91 mmol/mol]) were randomized to receive placebo or dapagliflozin 10 mg/day plus saxagliptin and metformin. The primary end point was the change in HbA(1c) from baseline to week 24. Secondary end points included fasting plasma glucose (FPG) level, 2-h postprandial glucose (PPG) level, body weight, and proportion of patients achieving an HbA(1c) level of <7% (53 mmol/mol). RESULTS Treatment with dapagliflozin add-on to saxagliptin plus metformin resulted in a greater mean HbA(1c) reduction than placebo (-0.82 vs. -0.10% [-9 vs. -1.1 mmol/mol], P < 0.0001). Significantly greater reductions in FPG level, 2-h PPG level, and body weight were observed, and more patients achieved an HbA(1c) level of < 7% (53 mmol/mol) with treatment with dapagliflozin versus placebo. Adverse events were similar across treatment groups, with a low overall risk of hypoglycemia (similar to 1%). Genital infections developed in more patients with dapagliflozin treatment (5%) than with placebo (0.6%). CONCLUSIONS Triple therapy with dapagliflozin add-on to saxagliptin plus metformin improves glycemic control and is well tolerated in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin therapy.
引用
收藏
页码:2009 / 2017
页数:9
相关论文
共 45 条
[1]   Approaches to Glycemic Treatment [J].
不详 .
DIABETES CARE, 2015, 38 :S41-S48
[2]   Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial [J].
Bailey, C. J. ;
Villegas, E. C. Morales ;
Woo, V. ;
Tang, W. ;
Ptaszynska, A. ;
List, J. F. .
DIABETIC MEDICINE, 2015, 32 (04) :531-541
[3]   Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial [J].
Bailey, Clifford J. ;
Gross, Jorge L. ;
Pieters, Anne ;
Bastien, Arnaud ;
List, James F. .
LANCET, 2010, 375 (9733) :2223-2233
[4]   Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with Type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study [J].
Bajaj, M. ;
Gilman, R. ;
Patel, S. ;
Kempthorne-Rawson, J. ;
Lewis-D'Agostino, D. ;
Woerle, H. -J. .
DIABETIC MEDICINE, 2014, 31 (12) :1505-1514
[5]   Comparative Effectiveness and Safety of Medications for Type 2 Diabetes: An Update Including New Drugs and 2-Drug Combinations [J].
Bennett, Wendy L. ;
Maruthur, Nisa M. ;
Singh, Sonal ;
Segal, Jodi B. ;
Wilson, Lisa M. ;
Chatterjee, Ranee ;
Marinopoulos, Spyridon S. ;
Puhan, Milo A. ;
Ranasinghe, Padmini ;
Block, Lauren ;
Nicholson, Wanda K. ;
Hutfless, Susan ;
Bass, Eric B. ;
Bolen, Shari .
ANNALS OF INTERNAL MEDICINE, 2011, 154 (09) :602-613
[6]   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 [J].
Chacra, A. R. ;
Tan, G. H. ;
Apanovitch, A. ;
Ravichandran, S. ;
List, J. ;
Chen, R. .
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, 2009, 63 (09) :1395-1406
[7]   Introduction [J].
Cheng, Alice Y. Y. .
CANADIAN JOURNAL OF DIABETES, 2013, 37 :S1-S3
[8]   Efficacy and Tolerability of the DPP-4 Inhibitor Alogliptin Combined with Pioglitazone, in Metformin-Treated Patients with Type 2 Diabetes [J].
DeFronzo, R. A. ;
Burant, C. F. ;
Fleck, P. ;
Wilson, C. ;
Mekki, Q. ;
Pratley, R. E. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (05) :1615-1622
[9]   Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes [J].
DeFronzo, Ralph A. ;
Hompesch, Marcus ;
Kasichayanula, Sreeneeranj ;
Liu, Xiaoni ;
Hong, Ying ;
Pfister, Marc ;
Morrow, Linda A. ;
Leslie, Bruce R. ;
Boulton, David W. ;
Ching, Agatha ;
LaCreta, Frank P. ;
Griffen, Steven C. .
DIABETES CARE, 2013, 36 (10) :3169-3176
[10]   The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes With Metformin Alone [J].
DeFronzo, Ralph A. ;
Hissa, Miguel N. ;
Garber, Alan J. ;
Gross, Jorge Luiz ;
Duan, Raina Yuyan ;
Ravichandran, Shoba ;
Chen, Roland S. .
DIABETES CARE, 2009, 32 (09) :1649-1655