Dapagliflozin Is Effective as Add-on Therapy to Sitagliptin With or Without Metformin: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

被引:239
作者
Jabbour, Serge A. [1 ]
Hardy, Elise [2 ]
Sugg, Jennifer [2 ]
Parikh, Shamik [2 ]
机构
[1] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA
[2] AstraZeneca, Wilmington, DE USA
关键词
INADEQUATE GLYCEMIC CONTROL; CLINICAL-TRIALS; TYPE-2; MANAGEMENT; ROSIGLITAZONE; HYPERGLYCEMIA; ASSOCIATION; GLIMEPIRIDE; ADJUSTMENT; EFFICACY;
D O I
10.2337/dc13-0467
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVETo assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin.RESEARCH DESIGN AND METHODSIn this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/day) metformin (1,500 mg/day).RESULTSBaseline HbA(1c) and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA(1c) levels (-0.5% [-4.9 mmol/mol]) versus placebo (0.0% [+0.4 mmol/mol]). Dapagliflozin reduced body weight versus placebo (-2.1 and -0.3 kg) and reduced HbA(1c) levels in patients with baseline values 8.0% (-0.8% [8.7 mmol/mol] and 0.0% [0.3 mmol/mol]) and fasting plasma glucose levels (-24.1 mg/dL [-1.3 mmol/L] and 3.8 mg/dL [0.2 mmol/L]). Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%).CONCLUSIONSThese results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.
引用
收藏
页码:740 / 750
页数:11
相关论文
共 26 条
[11]   Safety and efficacy of saxagliptin added to thiazolidinedione over 76 weeks in patients with type 2 diabetes mellitus [J].
Hollander, Priscilla L. ;
Li, Jia ;
Frederich, Robert ;
Allen, Elsie ;
Chen, Roland .
DIABETES & VASCULAR DISEASE RESEARCH, 2011, 8 (02) :125-135
[12]   Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach [J].
Inzucchi, Silvio E. ;
Bergenstal, Richard M. ;
Buse, John B. ;
Diamant, Michaela ;
Ferrannini, Ele ;
Nauck, Michael ;
Peters, Anne L. ;
Tsapas, Apostolos ;
Wender, Richard ;
Matthews, David R. .
DIABETES CARE, 2012, 35 (06) :1364-1379
[13]   THE HUMAN KIDNEY LOW-AFFINITY NA+/GLUCOSE COTRANSPORTER SGLT2 - DELINEATION OF THE MAJOR RENAL REABSORPTIVE MECHANISM FOR D-GLUCOSE [J].
KANAI, Y ;
LEE, WS ;
YOU, GF ;
BROWN, D ;
HEDIGER, MA .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (01) :397-404
[14]   Regulatory mechanisms of Na+/glucose cotransporters in renal proximal tubule cells [J].
Lee, Y. J. ;
Lee, Y. J. ;
Han, H. J. .
KIDNEY INTERNATIONAL, 2007, 72 :S27-S35
[15]   Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 Diabetes [J].
List, James F. ;
Woo, Vincent ;
Morales, Enrique ;
Tang, Weihua ;
Fiedorek, Fred T. .
DIABETES CARE, 2009, 32 (04) :650-657
[16]   Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes [J].
Nathan, David M. ;
Buse, John B. ;
Davidson, Mayer B. ;
Ferrannini, Ele ;
Holman, Rury R. ;
Sherwin, Robert ;
Zinman, Bernard .
DIABETES CARE, 2009, 32 (01) :193-203
[17]   Dapagliflozin Versus Glipizide as Add-on Therapy in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control With Metformin A randomized, 52-week, double-blind, active-controlled noninferiority trial [J].
Nauck, Michael A. ;
Del Prato, Stefano ;
Meier, Juris J. ;
Duran-Garcia, Santiago ;
Rohwedder, Katja ;
Elze, Martina ;
Parikh, Shamik J. .
DIABETES CARE, 2011, 34 (09) :2015-2022
[18]   Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study [J].
Pratley, Richard E. ;
Reusch, Jane E. -B. ;
Fleck, Penny R. ;
Wilson, Craig A. ;
Mekki, Qais .
CURRENT MEDICAL RESEARCH AND OPINION, 2009, 25 (10) :2361-2371
[19]   Islet β cell failure in type 2 diabetes [J].
Prentki, Marc ;
Nolan, Christopher J. .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (07) :1802-1812
[20]   Triple therapy in type 2 diabetes - Insulin glargine or rosiglitazone added to combmiation therapy of sulfonylurea plus metformin in insulin-naive patients [J].
Rosenstock, J ;
Sugimoto, D ;
Strange, P ;
Stewart, JA ;
Soltes-Rak, E ;
Dailey, G .
DIABETES CARE, 2006, 29 (03) :554-559