Trial Outcomes & Findings for Efficacy and Safety of Dapagliflozin in Combination With Metformin in Type 2 Diabetes Patients (NCT NCT00660907)

Last Updated: 2015-03-30

Results Overview

To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on the absolute change from baseline in HbA1c level after 52 weeks double-blind treatment in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg/day or higher doses of metformin therapy alone.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1217 participants

Primary outcome timeframe

Baseline to Week 52

Results posted on

2015-03-30

Participant Flow

The 1st patient was enrolled on 31 Mar 2008. The last patient last visit was on 15 Dec 2009. 1901 patients (pts) were screened and 1217 pts were enrolled with the aim to randomize 816. 2 randomized pts were excluded since they received no medication. Eventually, 814 pts received medication. This study was conducted at 95 centers world-wide.

For participants with a metformin dose of less than 1500 mg/day, a change in metformin dose in the past 8 weeks or on an Oral Anti-Diabetic (OAD), an 8-week metformin-only dose stabilisation period occurred. A 2-week placebo lead in period occurred after the dose stabilisation period or after enrolment if dose stabilisation period was skipped.

Participant milestones

Participant milestones
Measure	Dapagliflozin Plus Metformin Experimental dapagliflozin plus metformin	Glipizide Plus Metformin Active Comparator glipizide plus metformin
Overall Study STARTED	406	408
Overall Study COMPLETED	322	314
Overall Study NOT COMPLETED	84	94

Reasons for withdrawal

Reasons for withdrawal
Measure	Dapagliflozin Plus Metformin Experimental dapagliflozin plus metformin	Glipizide Plus Metformin Active Comparator glipizide plus metformin
Overall Study Incorrect Enrollment	1	1
Overall Study Adverse Event	33	19
Overall Study Subject No Longer Meets Study Criteria	6	27
Overall Study Withdrawal by Subject	23	32
Overall Study Lost to Follow-up	3	3
Overall Study Poor/Non-Compliance	5	1
Overall Study Safety	1	0
Overall Study Death	1	3
Overall Study Various	11	8

Baseline Characteristics

Efficacy and Safety of Dapagliflozin in Combination With Metformin in Type 2 Diabetes Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dapagliflozin Plus Metformin n=400 Participants Experimental dapagliflozin plus metformin	Glipizide Plus Metformin n=401 Participants Active Comparator glipizide plus metformin	Total n=801 Participants Total of all reporting groups
Age, Continuous	58.1 years STANDARD_DEVIATION 9.37 • n=5 Participants	58.6 years STANDARD_DEVIATION 9.80 • n=7 Participants	58.4 years STANDARD_DEVIATION 9.58 • n=5 Participants
Sex: Female, Male Female	179 Participants n=5 Participants	181 Participants n=7 Participants	360 Participants n=5 Participants
Sex: Female, Male Male	221 Participants n=5 Participants	220 Participants n=7 Participants	441 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	27 Participants n=5 Participants	34 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Race/Ethnicity, Customized White	327 Participants n=5 Participants	323 Participants n=7 Participants	650 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
BMI	31.71 kg/m2 STANDARD_DEVIATION 5.104 • n=5 Participants	31.23 kg/m2 STANDARD_DEVIATION 5.053 • n=7 Participants	31.47 kg/m2 STANDARD_DEVIATION 5.081 • n=5 Participants
HbA1c	7.69 percent STANDARD_DEVIATION 0.855 • n=5 Participants	7.74 percent STANDARD_DEVIATION 0.886 • n=7 Participants	7.72 percent STANDARD_DEVIATION 0.870 • n=5 Participants
FPG	162.24 ng/mL STANDARD_DEVIATION 37.796 • n=5 Participants	163.91 ng/mL STANDARD_DEVIATION 41.559 • n=7 Participants	163.07 ng/mL STANDARD_DEVIATION 39.708 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Full Analysis Set, participants with non-missing baseline and Week 52 (LOCF) values

Outcome measures

Outcome measures
Measure	Dapagliflozin Plus Metformin n=400 Participants Experimental dapagliflozin plus metformin	Glipizide Plus Metformin n=401 Participants Active Comparator glipizide plus metformin
Adjusted Mean Change in HbA1c Levels	-0.52 percent Interval -0.6 to -0.44	-0.52 percent Interval -0.6 to -0.44

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Full Analysis Set, participants with non-missing baseline and Week 52 (LOCF) values

To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight after 52 weeks double-blind treatment.

Outcome measures

Outcome measures
Measure	Dapagliflozin Plus Metformin n=400 Participants Experimental dapagliflozin plus metformin	Glipizide Plus Metformin n=401 Participants Active Comparator glipizide plus metformin
Adjusted Mean Change in Body Weight	-3.22 kg Interval -3.56 to -2.87	1.44 kg Interval 1.09 to 1.78

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Full analysis set

To assess the effect of dapagliflozin plus metformin treatment compared to glipizide plus metformin on the occurrence of hypoglycemic events. Least Squares Mean represents the percent of participants adjusted for HbA1c baseline value.

Outcome measures

Outcome measures
Measure	Dapagliflozin Plus Metformin n=400 Participants Experimental dapagliflozin plus metformin	Glipizide Plus Metformin n=401 Participants Active Comparator glipizide plus metformin
Proportion of Participants With at Least One Episode of Hypoglycemia	3.5 Percentage of participants Interval 1.7 to 5.3	40.8 Percentage of participants Interval 36.1 to 45.5

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Full Analysis Set, participants with non-missing baseline and Week 52 (LOCF) values

To evaluate the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight assessed by a reduction after 52 weeks of at least 5% compared to baseline. Least Squares Mean represents the percent of participants adjusted for baseline value.

Outcome measures

Outcome measures
Measure	Dapagliflozin Plus Metformin n=400 Participants Experimental dapagliflozin plus metformin	Glipizide Plus Metformin n=401 Participants Active Comparator glipizide plus metformin
Proportion of Participants With Body Weight Reduction of at Least 5%	33.3 Percentage of participants Interval 28.7 to 37.9	2.5 Percentage of participants Interval 1.0 to 4.0

Adverse Events

Dapagliflozin Plus Metformin

Serious events: 35 serious events

Other events: 163 other events

Deaths: 0 deaths

Glipizide Plus Metformin

Serious events: 46 serious events

Other events: 260 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Dapagliflozin Plus Metformin n=406 participants at risk Experimental dapagliflozin plus metformin	Glipizide Plus Metformin n=408 participants at risk Active Comparator glipizide plus metformin
Gastrointestinal disorders Diarrhoea	4.7% 19/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	6.4% 26/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.
Infections and infestations Nasopharyngitis	10.6% 43/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	15.0% 61/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.
Infections and infestations Upper Respiratory Tract Infection	5.9% 24/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	7.6% 31/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.
Infections and infestations Influenza	7.4% 30/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	7.4% 30/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.
Infections and infestations Urinary Tract Infection	7.4% 30/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	4.2% 17/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 11/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	5.1% 21/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.
Nervous system disorders Dizziness	3.7% 15/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	9.1% 37/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.
Nervous system disorders Tremor	0.25% 1/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	7.6% 31/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.
Nervous system disorders Headache	5.2% 21/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	4.2% 17/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.2% 5/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	6.6% 27/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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	7.4% 30/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	8.6% 35/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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	3.4% 14/406 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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.	39.7% 162/408 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including 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