Efficacy and Safety in Patients With Type 2 Diabetes Mellitus, Cardiovascular Disease and Hypertension

A 24-week, Multicentre, Randomised, Double-blind, Age-stratified, Placebo Controlled, Phase III Study With a 80-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin 10 mg Once Daily in Pts With T2DM, CV Disease and Hypertension Who Exhibit Inadequate Glycaemic Control on Usual Care

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01031680

Enrollment

922

Registered

2009-12-14

Start date

2010-02-28

Completion date

2012-12-31

Last updated

2013-10-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiovascular Disease, Hypertension, Inadequate Glycaemic Control, Type 2 Diabetes Mellitus

Keywords

dapagliflozin, diabetes, cardiovascular disease, hypertension

Brief summary

This study is carried out to assess whether dapagliflozin lowers blood glucose, body weight and blood pressure, when added to patients existing medications and how it compares with their usual treatment without added dapagliflozin. Safety data will be collected and analysed to confirm that treatment with dapagliflozin is safe and well tolerated in patients who have diabetes, cardiovascular disease and hypertension.

Interventions

DRUGDapagliflozin

10 mg tablet, oral, once daily, 24- week treatment and 80-week extension period

DRUGPlacebo

Matching placebo tablet, oral, once daily, 24- week treatment and 80-week extension period

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

45 Years to No maximum

Healthy volunteers

Inclusion criteria

* Type 2 diabetes mellitus. * Cardiovascular disease * Hypertension

Exclusion criteria

* Patients with type 1 diabetes or diabetes insipidus * Patients with 3 or more oral anti-hyperglycaemic drugs with or without insulin and/or poorly controlled diabetes * Any clinically significant illness, which would compromise the patient's safety and their participation in the study

Design outcomes

Primary

Measure	Time frame	Description
Adjusted Mean Change in HbA1c Levels	Baseline to Week 24	To compare the glycemic efficacy of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease and hypertension, measured as the mean change in HbA1c from baseline to week 24.
Proportion of Responders Meeting All Criteria of a 3-item Endpoint of Clinical Benefit	Baseline to week 24	To compare the clinical benefit of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease and hypertension at week 24, measured as the proportion of responders for a 3-item endpoint of clinical benefit, defined as an absolute drop of 0.5% or more from baseline HbA1c, and a relative drop of 3% or more from baseline for total body weight, and an absolute drop of 3 mmHg or more from baseline in seated systolic blood pressure.

Secondary

Measure	Time frame	Description
Adjusted Mean Change in Seated Systolic Blood Pressure (SBP)	Baseline to Week 8	To compare the mean change in seated systolic blood pressure from baseline to week 8 between dapagliflozin 10 mg versus placebo.
Adjusted Mean Percent Change in Body Weight	Baseline to Week 24	To compare the mean percent change in body weight from baseline to week 24 between dapagliflozin 10 mg versus placebo.
Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 24 (LOCF)	Baseline to Week 24	To compare the mean change in seated systolic blood pressure from baseline to week 24 between dapagliflozin 10 mg versus placebo.
Proportion of Participants With a Reduction From Baseline of 5% or More in Body Weight in Participants With Baseline BMI ≥27 kg/m²	Baseline to Week 24	To compare the proportion of participants with BMI baseline ≥27 kg/m2 with a reduction from baseline of 5% or more in body weight with dapagliflozin 10 mg versus placebo from baseline to week 24. Least Squares Mean represents the percent of participants adjusted for baseline body weight and age stratum.

Countries

Argentina, Canada, Germany, Romania, Slovakia, Spain, Taiwan, United States, Vietnam

Participant flow

Recruitment details

First participant enrolled: 10 Feb 2010, last participant for last visit for the 24-week period: 26 May 2011. This study was conducted in 4 European countries, 2 countries in Asia/the Pacific Region, The United States, Canada, and Argentina. In total 1429 participants were enrolled and 922 participants were randomized.

Pre-assignment details

During a placebo lead-in period, participants were counselled on dietary and life-style modifications.

Participants by arm

Arm	Count
Experimental Dapagliflozin, 10 mg tablet, oral, once daily	455
Placebo Comparator Placebo, Matching placebo tablet, oral, once daily	459
Total	914

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Administrative Reason by Sponsor	0	1
Overall Study	Adverse Event	8	3
Overall Study	Death	2	1
Overall Study	Incorrect Enrolment	1	2
Overall Study	Lost to Follow-up	2	10
Overall Study	Poor/Non-compliance	5	6
Overall Study	Safety	1	0
Overall Study	Subject No Longer Meets Study Criteria	26	17
Overall Study	Various	0	2
Overall Study	Withdrawal by Subject	12	16

Baseline characteristics

Characteristic	Experimental	Placebo Comparator	Total
Age Continuous	62.8 Years STANDARD_DEVIATION 6.97	63.0 Years STANDARD_DEVIATION 7.66	62.9 Years STANDARD_DEVIATION 7.32
Age, Customized <55	58 Participants	74 Participants	132 Participants
Age, Customized >=55 and <65	205 Participants	189 Participants	394 Participants
Age, Customized >=65 and <75	164 Participants	165 Participants	329 Participants
Age, Customized >=75	28 Participants	31 Participants	59 Participants
Body Mass Index (BMI) < 25 kg/m²	29 Participants	30 Participants	59 Participants
Body Mass Index (BMI) >= 25 kg/m²	426 Participants	429 Participants	855 Participants
Body Mass Index (BMI) >= 27 kg/m²	388 Participants	397 Participants	785 Participants
Body Mass Index (BMI) >= 30 kg/m²	291 Participants	304 Participants	595 Participants
Haemoglobin A1c (HbA1c)	8.18 Percent STANDARD_DEVIATION 0.841	8.08 Percent STANDARD_DEVIATION 0.802	8.13 Percent STANDARD_DEVIATION 0.823
Seated Systolic Blood Pressure	133.5 mm Hg STANDARD_DEVIATION 13.48	133.0 mm Hg STANDARD_DEVIATION 13.81	133.2 mm Hg STANDARD_DEVIATION 13.64
Sex: Female, Male Female	146 Participants	144 Participants	290 Participants
Sex: Female, Male Male	309 Participants	315 Participants	624 Participants
Total Body Weight	92.63 kg STANDARD_DEVIATION 20.504	93.59 kg STANDARD_DEVIATION 19.467	93.11 kg STANDARD_DEVIATION 19.985

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	89 / 460	84 / 462
serious Total, serious adverse events	27 / 460	26 / 462

Outcome results

Primary

Adjusted Mean Change in HbA1c Levels

To compare the glycemic efficacy of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease and hypertension, measured as the mean change in HbA1c from baseline to week 24.

Time frame: Baseline to Week 24

Population: Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Experimental	Adjusted Mean Change in HbA1c Levels	-0.38 Percent
Placebo Comparator	Adjusted Mean Change in HbA1c Levels	0.08 Percent

Comparison: H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0p-value: <0.000195% CI: [-0.56, -0.37]ANCOVA

Primary

Proportion of Responders Meeting All Criteria of a 3-item Endpoint of Clinical Benefit

To compare the clinical benefit of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease and hypertension at week 24, measured as the proportion of responders for a 3-item endpoint of clinical benefit, defined as an absolute drop of 0.5% or more from baseline HbA1c, and a relative drop of 3% or more from baseline for total body weight, and an absolute drop of 3 mmHg or more from baseline in seated systolic blood pressure.

Time frame: Baseline to week 24

Population: Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Arm	Measure	Value (NUMBER)
Experimental	Proportion of Responders Meeting All Criteria of a 3-item Endpoint of Clinical Benefit	11.7 Percentage of participants
Placebo Comparator	Proportion of Responders Meeting All Criteria of a 3-item Endpoint of Clinical Benefit	0.9 Percentage of participants

Comparison: H0: proportion(treat) minus proportion(placebo) = 0 versus the alternative HA: proportion(treat) minus proportion(placebo) =/= 0p-value: <0.000195% CI: [7, 12.9]Cochran-Mantel-Haenszel

Secondary

Adjusted Mean Change in Seated Systolic Blood Pressure (SBP)

To compare the mean change in seated systolic blood pressure from baseline to week 8 between dapagliflozin 10 mg versus placebo.

Time frame: Baseline to Week 8

Population: Full Analysis Set, participants with non-missing baseline and Week 8 (LOCF) values

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Experimental	Adjusted Mean Change in Seated Systolic Blood Pressure (SBP)	-2.96 mmHg
Placebo Comparator	Adjusted Mean Change in Seated Systolic Blood Pressure (SBP)	-0.99 mmHg

Comparison: H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0p-value: 0.012695% CI: [-3.52, -0.42]ANCOVA

Secondary

Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 24 (LOCF)

To compare the mean change in seated systolic blood pressure from baseline to week 24 between dapagliflozin 10 mg versus placebo.

Time frame: Baseline to Week 24

Population: Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Experimental	Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 24 (LOCF)	-2.99 mmHg
Placebo Comparator	Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 24 (LOCF)	-1.03 mmHg

Comparison: H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0p-value: 0.017495% CI: [-3.56, -0.34]ANCOVA

Secondary

Adjusted Mean Percent Change in Body Weight

To compare the mean percent change in body weight from baseline to week 24 between dapagliflozin 10 mg versus placebo.

Time frame: Baseline to Week 24

Population: Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Experimental	Adjusted Mean Percent Change in Body Weight	-2.56 Percentage of Body Weight
Placebo Comparator	Adjusted Mean Percent Change in Body Weight	-0.30 Percentage of Body Weight

Comparison: H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0p-value: <0.000195% CI: [-2.64, -1.89]ANCOVA

Secondary

Proportion of Participants With a Reduction From Baseline of 5% or More in Body Weight in Participants With Baseline BMI ≥27 kg/m²

To compare the proportion of participants with BMI baseline ≥27 kg/m2 with a reduction from baseline of 5% or more in body weight with dapagliflozin 10 mg versus placebo from baseline to week 24. Least Squares Mean represents the percent of participants adjusted for baseline body weight and age stratum.

Time frame: Baseline to Week 24

Population: Full analysis set; participants with baseline BMI ≥27 kg/m² and Week 24 (LOCF) body weight value

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Experimental	Proportion of Participants With a Reduction From Baseline of 5% or More in Body Weight in Participants With Baseline BMI ≥27 kg/m²	16.5 Percentage of participants
Placebo Comparator	Proportion of Participants With a Reduction From Baseline of 5% or More in Body Weight in Participants With Baseline BMI ≥27 kg/m²	4.0 Percentage of participants

Comparison: H0: proportion(treat) minus proportion(placebo) = 0 versus the alternative HA: proportion(treat) minus proportion(placebo) =/= 0p-value: <0.000195% CI: [8.3, 16.6]Regression, Logistic

Source: ClinicalTrials.gov · Data processed: Mar 13, 2026

Efficacy and Safety in Patients With Type 2 Diabetes Mellitus, Cardiovascular Disease and Hypertension

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Adjusted Mean Change in HbA1c Levels

Proportion of Responders Meeting All Criteria of a 3-item Endpoint of Clinical Benefit

Adjusted Mean Change in Seated Systolic Blood Pressure (SBP)

Adjusted Mean Change in Seated Systolic Blood Pressure (SBP) at Week 24 (LOCF)

Adjusted Mean Percent Change in Body Weight

Proportion of Participants With a Reduction From Baseline of 5% or More in Body Weight in Participants With Baseline BMI ≥27 kg/m²