Trial Outcomes & Findings for Efficacy and Safety of Dapagliflozin in Combination With Glimepiride (a Sulphonylurea) in Type 2 Diabetes Patients (NCT NCT00680745)

Last Updated: 2013-10-14

Results Overview

To assess the efficacy of dapagliflozin compared to placebo as add-on therapy to glimepiride in improving glycemic control in participants with type 2 diabetes, as determined by the change in HbA1C levels from baseline to the end of the 24-week double-blind treatment period.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

597 participants

Primary outcome timeframe

Baseline to Week 24

Results posted on

2013-10-14

Participant Flow

Enrollment: 859 (597 randomized and 592 in the Full Analysis Set) Study Start Date:April 2008 Study Completion Date:May 2010 Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)

Reasons for enrolled participants not being randomised: 229 incorrect enrollment, 4 adverse event, 23 withdrew consent, 2 lost to follow up and 4 other.

Participant milestones

Participant milestones
Measure	Dapagliflozin 2.5mg + Glimepiride Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride Dapagliflozin tablet 10 mg once daily plus glimepiride	Placebo + Glimepiride Placebo comparator plus glimepiride
Overall Study STARTED	154	145	151	146
Overall Study COMPLETED	140	132	141	133
Overall Study NOT COMPLETED	14	13	10	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Dapagliflozin 2.5mg + Glimepiride Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride Dapagliflozin tablet 10 mg once daily plus glimepiride	Placebo + Glimepiride Placebo comparator plus glimepiride
Overall Study Withdrawal by Subject	8	3	2	8
Overall Study Lost to Follow-up	0	1	1	0
Overall Study Death	1	0	1	0
Overall Study Adverse Event	5	3	3	3
Overall Study Poor/Non-compliance	0	3	0	0
Overall Study Subject No Longer Meets Study Criteria	0	2	0	2
Overall Study False Treatment	0	1	3	0

Baseline Characteristics

Efficacy and Safety of Dapagliflozin in Combination With Glimepiride (a Sulphonylurea) in Type 2 Diabetes Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dapagliflozin 2.5mg + Glimepiride n=154 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride n=142 Participants Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride n=151 Participants Dapagliflozin tablet 10 mg once daily plus glimepiride	Placebo + Glimepiride n=145 Participants Placebo comparator plus glimepiride	Total n=592 Participants Total of all reporting groups
Age Continuous	59.9 years STANDARD_DEVIATION 10.14 • n=5 Participants	60.2 years STANDARD_DEVIATION 9.73 • n=7 Participants	58.9 years STANDARD_DEVIATION 8.32 • n=5 Participants	60.3 years STANDARD_DEVIATION 10.16 • n=4 Participants	59.8 years STANDARD_DEVIATION 9.60 • n=21 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	71 Participants n=7 Participants	85 Participants n=5 Participants	74 Participants n=4 Participants	307 Participants n=21 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	71 Participants n=7 Participants	66 Participants n=5 Participants	71 Participants n=4 Participants	285 Participants n=21 Participants
Race/Ethnicity, Customized White	108 Participants n=5 Participants	96 Participants n=7 Participants	106 Participants n=5 Participants	101 Participants n=4 Participants	411 Participants n=21 Participants
Race/Ethnicity, Customized Asian	46 Participants n=5 Participants	46 Participants n=7 Participants	45 Participants n=5 Participants	44 Participants n=4 Participants	181 Participants n=21 Participants
BMI	30.01 kg/m2 STANDARD_DEVIATION 5.120 • n=5 Participants	29.84 kg/m2 STANDARD_DEVIATION 5.182 • n=7 Participants	29.75 kg/m2 STANDARD_DEVIATION 5.641 • n=5 Participants	29.74 kg/m2 STANDARD_DEVIATION 4.569 • n=4 Participants	29.84 kg/m2 STANDARD_DEVIATION 5.135 • n=21 Participants
HbA1c	8.11 Percent STANDARD_DEVIATION 0.749 • n=5 Participants	8.12 Percent STANDARD_DEVIATION 0.781 • n=7 Participants	8.07 Percent STANDARD_DEVIATION 0.790 • n=5 Participants	8.15 Percent STANDARD_DEVIATION 0.736 • n=4 Participants	8.11 Percent STANDARD_DEVIATION 0.763 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

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

Outcome measures

Outcome measures
Measure	Dapagliflozin 2.5mg + Glimepiride n=154 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride n=142 Participants Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride n=150 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Placebo + Glimepiride n=143 Participants Placebo comparator plus glimepiride
Adjusted Mean Change in HbA1c Levels	-0.58 Percent Interval -0.69 to -0.46	-0.63 Percent Interval -0.75 to -0.5	-0.82 Percent Interval -0.94 to -0.7	-0.13 Percent Interval -0.26 to -0.01

SECONDARY outcome

Timeframe: Baseline to Week 24

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

To show that dapagliflozin plus glimepiride results in greater reduction in body weight or less weight gain after 24 weeks of treatment when compared to placebo plus glimepiride.

Outcome measures

Outcome measures
Measure	Dapagliflozin 2.5mg + Glimepiride n=154 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride n=142 Participants Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride n=151 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Placebo + Glimepiride n=145 Participants Placebo comparator plus glimepiride
Adjusted Mean Change in Body Weight	-1.18 kg Interval -1.62 to -0.75	-1.56 kg Interval -2.01 to -1.11	-2.26 kg Interval -2.7 to -1.83	-0.72 kg Interval -1.16 to -0.28

SECONDARY outcome

Timeframe: Baseline to Week 24

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

To show that dapagliflozin plus glimepiride results in greater reductions in the 2-h post-challenge plasma glucose rise as a response to an oral glucose tolerance test (OGTT) from baseline to Week 24.

Outcome measures

Outcome measures
Measure	Dapagliflozin 2.5mg + Glimepiride n=126 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride n=117 Participants Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride n=132 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Placebo + Glimepiride n=109 Participants Placebo comparator plus glimepiride
Adjusted Mean Change in 2-h Post-challenge Plasma Glucose Rise	-37.5 mg/dL Interval -46.7 to -28.3	-32.0 mg/dL Interval -41.5 to -22.5	-34.9 mg/dL Interval -43.8 to -25.9	-6.0 mg/dL Interval -15.8 to 3.9

SECONDARY outcome

Timeframe: At Week 24

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

To show that dapagliflozin plus glimepiride results in a larger proportion of participants achieving a therapeutic glycemic response, defined as HbA1c \< 7% after 24 weeks of treatment, compared to placebo plus glimepiride.

Outcome measures

Outcome measures
Measure	Dapagliflozin 2.5mg + Glimepiride n=154 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride n=142 Participants Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride n=150 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Placebo + Glimepiride n=143 Participants Placebo comparator plus glimepiride
Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7%	26.8 Percentage of participants Interval 20.2 to 33.3	30.3 Percentage of participants Interval 23.4 to 37.1	31.7 Percentage of participants Interval 24.7 to 38.7	13.0 Percentage of participants Interval 7.6 to 18.4

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Full Analysis Set, participants with baseline BMI of 27 kg/m2 or more and Week 24 (LOCF) body weight value

To show that dapagliflozin plus glimepiride results in greater reductions in body weight or less weight gain in participants with baseline BMI ≥27 kg/m2 after 24 weeks of treatment when compared to placebo plus glimepiride.

Outcome measures

Outcome measures
Measure	Dapagliflozin 2.5mg + Glimepiride n=104 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride n=97 Participants Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride n=99 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Placebo + Glimepiride n=103 Participants Placebo comparator plus glimepiride
Adjusted Mean Change in Body Weight for Participants With Baseline Body Mass Index (BMI)≥27 kg/m2	-1.17 kg Interval -1.75 to -0.59	-1.74 kg Interval -2.34 to -1.15	-2.47 kg Interval -3.06 to -1.88	-0.80 kg Interval -1.38 to -0.22

SECONDARY outcome

Timeframe: Baseline to Week 24

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

To show that dapagliflozin plus glimepiride leads to greater reductions in FPG after 24 weeks of treatment compared to placebo plus glimepiride.

Outcome measures

Outcome measures
Measure	Dapagliflozin 2.5mg + Glimepiride n=154 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride n=142 Participants Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride n=150 Participants Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Placebo + Glimepiride n=145 Participants Placebo comparator plus glimepiride
Adjusted Mean Change in Fasting Plasma Glucose (FPG)	-16.8 mg/dL Interval -21.7 to -12.0	-21.2 mg/dL Interval -26.3 to -16.2	-28.5 mg/dL Interval -33.4 to -23.6	-2.0 mg/dL Interval -6.9 to 3.0

Adverse Events

Dapagliflozin 2.5mg + Glimepiride

Serious events: 11 serious events

Other events: 22 other events

Deaths: 0 deaths

Dapagliflozin 5mg + Glimepiride

Serious events: 10 serious events

Other events: 19 other events

Deaths: 0 deaths

Dapagliflozin 10mg + Glimepiride

Serious events: 9 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo + Glimepiride

Serious events: 7 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Dapagliflozin 2.5mg + Glimepiride n=154 participants at risk Dapagliflozin tablet 2.5 mg once daily plus glimepiride	Dapagliflozin 5mg + Glimepiride n=145 participants at risk Dapagliflozin tablet 5 mg once daily plus glimepiride	Dapagliflozin 10mg + Glimepiride n=151 participants at risk Dapagliflozin tablet 10 mg once daily plus glimepiride	Placebo + Glimepiride n=146 participants at risk Placebo comparator plus glimepiride
Infections and infestations NASOPHARYNGITIS	1.9% 3/154 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.	5.5% 8/145 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.	3.3% 5/151 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.	2.7% 4/146 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
Vascular disorders HYPERTENSION	5.2% 8/154 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.	1.4% 2/145 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.	1.3% 2/151 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.	4.1% 6/146 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
Endocrine disorders Hypoglycemia	7.1% 11/154 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.	6.9% 10/145 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.	7.9% 12/151 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.	4.8% 7/146 • Non-serious/serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment period plus 4/30 days or up to follow-up visit if earlier, or up to and incl the start date of extension period if earlier. Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.

Additional Information

Eva Johnsson

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an Investigator requests permission to publish data from this study any such publication is to be agreed with AstraZeneca (AZ) in advance. The investigator agrees to provide AZ as soon as possible with drafts of proposed publications. Unless otherwise agreed, AZ shall have a period of 60 days from receipt of the proposed final manuscript to review it and may within such time require that submission for publication of the manuscript be delayed in order for AZ to file patent applications.
Publication restrictions are in place

Restriction type: OTHER