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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

A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled, International Phase III Study With a 28-week Extension Period to Evaluate the Safety and Efficacy of Dapagliflozin 10mg Once Daily in Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on a Background Combination of Metformin and Sulfonylurea

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01392677
Enrollment
311
Registered
2011-07-12
Start date
2011-10-31
Completion date
2013-08-31
Last updated
2014-03-12

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

Conditions

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

Keywords

dapagliflozin, diabetes, hyperglycaemia

Brief summary

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.

Interventions

DRUGdapagliflozin

10 mg tablet, oral, once daily, 24- week treatment and 28- week extension period

DRUGplacebo

matching placebo tablet, oral, once daily, 24- week treatment and 28- week extension period

Sponsors

Bristol-Myers Squibb
CollaboratorINDUSTRY
AstraZeneca
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Adjusted Mean Change From Baseline in HbA1c LevelsBaseline to week 24To compare the change from baseline in HbA1c to week 24 between dapagliflozin 10 mg in combination with metformin and sulfonylurea and placebo in combination with metformin and sulfonylurea.

Secondary

MeasureTime frameDescription
Adjusted Mean Change From Baseline in FPGBaseline to week 24To compare the change from baseline in fasting plasma glucose (FPG) to week 24 (LOCF) between dapagliflozin and placebo
Adjusted Mean Change From Baseline in Total Body WeightBaseline to week 24To compare the change from baseline in total body weight to week 24 (LOCF) between dapagliflozin and placebo
Proportion of Participants With HbA1c Value < 7.0% at Week 24 (LOCF)Baseline to week 24To compare the proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c \<7.0%, at week 24 (LOCF) between dapagliflozin and placebo
Adjusted Mean Change From Baseline in Seated Systolic Blood PressureBaseline to week 8To compare the change from baseline in seated systolic blood pressure (SBP) to week 8 (LOCF) between dapagliflozin and placebo

Countries

Canada, Czechia, Germany, Poland, Slovakia, Spain

Participant flow

Recruitment details

First participant enrolled: 24 Oct 2011. Last participant completed 24 week period: 07 Jan 2013. 311 participants were enrolled, 219 were randomized in 45 centers in 5 European countries and in North America. Men and women aged \>= 18 years with inadequate glycemic control (HbA1c 7.0% to 10.5% prior to randomization).

Pre-assignment details

During enrollment, diet and life-style advice was given to participants and was reinforced during a placebo lead-in period. Dose of anti-hyperglycemic combination therapy of metformin \>= 1500 mg/day and maximum tolerated dose which must be at least half the maximum dose of sulfonylurea for at least 8 weeks prior to enrollment were to remain stable.

Participants by arm

ArmCount
Placebo Plus Metformin Plus Sulfonylurea
Placebo once daily plus background combination of metformin and sulfonylurea
108
Dapagliflozin 10mg Plus Metformin Plus Sulfonylurea
Dapagliflozin 10mg once daily plus background combination of metformin and sulfonylurea
108
Total216

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event31
Overall StudyIncorrect enrollment23
Overall StudyOther reason32
Overall StudyWithdrawal by Subject02

Baseline characteristics

CharacteristicDapagliflozin 10mg Plus Metformin Plus SulfonylureaTotalPlacebo Plus Metformin Plus Sulfonylurea
Age, Continuous61.1 Years
STANDARD_DEVIATION 9.65
61.0 Years
STANDARD_DEVIATION 9.42
60.9 Years
STANDARD_DEVIATION 9.24
Body Mass Index31.93 kg/m^2
STANDARD_DEVIATION 4.84
31.97 kg/m^2
STANDARD_DEVIATION 4.702
32.02 kg/m^2
STANDARD_DEVIATION 4.581
Body Weight88.57 kg
STANDARD_DEVIATION 17.584
89.32 kg
STANDARD_DEVIATION 16.872
90.07 kg
STANDARD_DEVIATION 16.175
Fasting C-Peptide2.5 ng/mL
STANDARD_DEVIATION 1.06
2.5 ng/mL
STANDARD_DEVIATION 1.02
2.5 ng/mL
STANDARD_DEVIATION 0.98
Fasting Plasma Glucose167.4 mg/dL
STANDARD_DEVIATION 43.32
173.8 mg/dL
STANDARD_DEVIATION 43.61
180.2 mg/dL
STANDARD_DEVIATION 43.13
Glycosylated hemoglobin A1c (HbA1c)8.08 Percent
STANDARD_DEVIATION 0.912
8.16 Percent
STANDARD_DEVIATION 0.89
8.24 Percent
STANDARD_DEVIATION 0.865
Race/Ethnicity, Customized
Asian
3 Participants7 Participants4 Participants
Race/Ethnicity, Customized
Black/African American
0 Participants1 Participants1 Participants
Race/Ethnicity, Customized
Other
1 Participants2 Participants1 Participants
Race/Ethnicity, Customized
White
104 Participants206 Participants102 Participants
Sex: Female, Male
Female
62 Participants110 Participants48 Participants
Sex: Female, Male
Male
46 Participants106 Participants60 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
7 / 1095 / 109
serious
Total, serious adverse events
6 / 1091 / 109

Outcome results

Primary

Adjusted Mean Change From Baseline in HbA1c Levels

To compare the change from baseline in HbA1c to week 24 between dapagliflozin 10 mg in combination with metformin and sulfonylurea and placebo in combination with metformin and sulfonylurea.

Time frame: Baseline to week 24

Population: Full Analysis Set, participants with non-missing baseline and week 24 values

ArmMeasureValue (LEAST_SQUARES_MEAN)
Placebo Plus Metformin Plus SulfonylureaAdjusted Mean Change From Baseline in HbA1c Levels-0.17 Percent
Dapagliflozin 10mg Plus Metformin Plus SulfonylureaAdjusted Mean Change From Baseline in HbA1c Levels-0.86 Percent
Comparison: H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0p-value: <0.000195% CI: [-0.89, -0.49]Mixed Models Analysis
Secondary

Adjusted Mean Change From Baseline in FPG

To compare the change from baseline in fasting plasma glucose (FPG) to week 24 (LOCF) between dapagliflozin and placebo

Time frame: Baseline to week 24

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

ArmMeasureValue (LEAST_SQUARES_MEAN)
Placebo Plus Metformin Plus SulfonylureaAdjusted Mean Change From Baseline in FPG-0.78 mg/dL
Dapagliflozin 10mg Plus Metformin Plus SulfonylureaAdjusted Mean Change From Baseline in FPG-34.23 mg/dL
Comparison: H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0p-value: <0.000195% CI: [-43.08, -23.82]ANCOVA
Secondary

Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure

To compare the change from baseline in seated systolic blood pressure (SBP) to week 8 (LOCF) between dapagliflozin and placebo

Time frame: Baseline to week 8

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

ArmMeasureValue (LEAST_SQUARES_MEAN)
Placebo Plus Metformin Plus SulfonylureaAdjusted Mean Change From Baseline in Seated Systolic Blood Pressure-0.27 mmHg
Dapagliflozin 10mg Plus Metformin Plus SulfonylureaAdjusted Mean Change From Baseline in Seated Systolic Blood Pressure-4.04 mmHg
Comparison: H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0p-value: 0.02595% CI: [-7.05, -0.48]ANCOVA
Secondary

Adjusted Mean Change From Baseline in Total Body Weight

To compare the change from baseline in total body weight to week 24 (LOCF) between dapagliflozin and placebo

Time frame: Baseline to week 24

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

ArmMeasureValue (LEAST_SQUARES_MEAN)
Placebo Plus Metformin Plus SulfonylureaAdjusted Mean Change From Baseline in Total Body Weight-0.58 kg
Dapagliflozin 10mg Plus Metformin Plus SulfonylureaAdjusted Mean Change From Baseline in Total Body Weight-2.65 kg
Comparison: H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0p-value: <0.000195% CI: [-2.79, -1.35]ANCOVA
Secondary

Proportion of Participants With HbA1c Value < 7.0% at Week 24 (LOCF)

To compare the proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c \<7.0%, at week 24 (LOCF) between dapagliflozin and placebo

Time frame: Baseline to week 24

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

ArmMeasureValue (LEAST_SQUARES_MEAN)
Placebo Plus Metformin Plus SulfonylureaProportion of Participants With HbA1c Value < 7.0% at Week 24 (LOCF)11.1 Percentage of participants
Dapagliflozin 10mg Plus Metformin Plus SulfonylureaProportion of Participants With HbA1c Value < 7.0% at Week 24 (LOCF)31.8 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: [10.7, 30.6]Regression, Logistic

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026