Evaluation of Safety and Efficacy of Dapagliflozin in Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Background Combination of Metformin and Sulfonylurea

• Change in fasting plasma glucose from baseline to week 24 [ Time Frame: from baseline to week 24 ] [ Designated as safety issue: No ]
• Change in total body weight from baseline to week 24 [ Time Frame: from baseline to week 24 ] [ Designated as safety issue: No ]
• Proportion of patients achieving a therapeutic glycaemic response, defined as HbA1c <7.0% at week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
• Change in seated systolic blood pressure (SBP) from baseline to week 8 [ Time Frame: from baseline to week 8 ] [ Designated as safety issue: No ]

• Change in fasting plasma glucose from baseline to week 24 [ Time Frame: from baseline to week 24 ] [ Designated as safety issue: No ]
• Change in total body weight from baseline to week 24 [ Time Frame: from baseline to week 24 ] [ Designated as safety issue: No ]
• Proportion of patients achieving a therapeutic glycaemic response, defined as HbA1c <7.0% at week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
• Change in seated systolic blood pressure (SBP) from baseline to week 8 [ Time Frame: from baseline to week 8 ] [ Designated as safety issue: No ]
• Proportion of patients discontinued for lack of efficacy or rescued for failing to maintain FPG below pre-specified rescue criteria at weeks 4, 8, 16 and 24 between dapagliflozin and placebo. [ Time Frame: At weeks 4,8,16,24 ] [ Designated as safety issue: No ]
• Change from baseline in HbA1c to week 24 between dapagliflozin and placebo in patients with baseline HbA1c ≥8.0 %. [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: No ]
• Change from baseline in HbA1c to week 24 between dapagliflozin and placebo in patients with baseline HbA1c ≥9.0%. [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: No ]
• Change from baseline in FPG to week 8 between dapagliflozin and placebo [ Time Frame: From baseline to week 8 ] [ Designated as safety issue: No ]
• Change from baseline in seated SBP to week 24 between dapagliflozin and placebo. [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: No ]
• Proportion of patients who achieve seated BP of <130/80mmHg at week 24 in patients with baseline elevated blood pressure (BP) (baseline SBP ≥130 mmHg and/or baseline diastolic blood pressure (DBP) ≥80mmHg). [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
• Percent change from baseline in fasting lipids (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) to week 24 between dapagliflozin and placebo. [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: No ]
• Change from baseline in HOMA-2, HOMA-IR to week 24 between dapagliflozin and placebo. [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: No ]
• Change from baseline in insulin, proinsulin and C-peptide values to week 24 between dapagliflozin and placebo [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: No ]
• Change from baseline in waist circumference to week 24 between dapagliflozin and placebo. [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: No ]
• Effect of dapagliflozin versus placebo from baseline to week 24 on health-related quality of life (HRQL) as measured by Euro quality of life 5 Dimensions 3 Levels (EQ-5D-3L). [ Time Frame: From baseline to week 24 ] [ Designated as safety issue: No ]
• Scores of treatment satisfaction, individual satisfaction and perceived frequency of hyper/hypoglycaemia as measured by Diabetes Treatment Satisfaction Questionnaire status (DTSQs) observed with dapagliflozin vs. placebo from baseline to wk 24 and wk 52. [ Time Frame: From baseline to week 24 and week 52 ] [ Designated as safety issue: No ]

This study intends to compare the efficacy and safety of dapagliflozin versus placebo in patients with type 2 diabetes who have inadequate glycaemic control on a background combination of metformin and sulfonylurea.

• Type 2 Diabetes Mellitus
• High HbA1c Level
• Inadequate Glycaemic Control

• Drug: dapagliflozin
  10 mg tablet, oral, once daily, 24- week treatment and 28- week extension period
• Drug: placebo
  matching placebo tablet, oral, once daily, 24- week treatment and 28- week extension period

• Experimental: Dapagliflozin 10 mg tablet
  Intervention: Drug: dapagliflozin
• Placebo Comparator: matching placebo tablet
  Intervention: Drug: placebo

Inclusion Criteria:

• Type 2 diabetes mellitus
• Men or women age ≥ 18 years old
• Stable dose combination of metformin and sulfonylurea
• HbA1c ≥7.7% and ≤11.0%

Exclusion Criteria:

• Type 1 diabetes mellitus or diabetes insipidus
• Recent cardiovascular events
• Kidney or urological disorders
• Hepatic disorders