Trial Outcomes & Findings for Evaluation of the Effect of Dapagliflozin in Combination With Metformin on Body Weight in Subjects With Type 2 Diabetes (NCT NCT00855166)
NCT ID: NCT00855166
Last Updated: 2013-10-14
Results Overview
To evaluate the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin on total body weight after 24 weeks of oral administration of double-blind treatment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
182 participants
Primary outcome timeframe
Baseline to Week 24
Results posted on
2013-10-14
Participant Flow
First participant enrolled: 13 Feb 2009. Last participant completed 24 week period: 03 Jun 2010. 314 participants were enrolled, 182 were randomized in 40 centers in 5 European countries. Men aged 30-75 years and women aged 55-75 years with inadequate glycemic control (HbA1c 6.5% to 8.5%), BMI of at least 25 kg/sqm and body weight \<= 120 kg.
During a placebo lead-in period, participants were counselled on dietary and life-style modifications. The metformin dose was adjusted to open label 1500 mg/day, 2000 mg/day or 2500 mg/day. Neither gender should exceed 60% of the total number of randomized participants.
Participant milestones
| Measure |
Placebo Plus Metformin
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Overall Study
COMPLETED
|
86
|
83
|
|
Overall Study
STARTED
|
91
|
91
|
|
Overall Study
NOT COMPLETED
|
5
|
8
|
Reasons for withdrawal
| Measure |
Placebo Plus Metformin
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
4
|
|
Overall Study
Poor/non-compliance
|
2
|
0
|
|
Overall Study
Administrative reasons by sponsor
|
1
|
0
|
|
Overall Study
Subject no longer meets study criteria
|
1
|
1
|
Baseline Characteristics
Evaluation of the Effect of Dapagliflozin in Combination With Metformin on Body Weight in Subjects With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Placebo Plus Metformin
n=91 Participants
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=89 Participants
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
Total
n=180 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
60.8 Years
STANDARD_DEVIATION 6.82 • n=5 Participants
|
60.6 Years
STANDARD_DEVIATION 8.16 • n=7 Participants
|
60.7 Years
STANDARD_DEVIATION 7.49 • n=5 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
91 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
180 Participants
n=5 Participants
|
|
Body Weight
|
90.91 Kilogram
STANDARD_DEVIATION 13.716 • n=5 Participants
|
92.06 Kilogram
STANDARD_DEVIATION 14.128 • n=7 Participants
|
91.48 Kilogram
STANDARD_DEVIATION 13.894 • n=5 Participants
|
|
Body Mass Index
|
31.68 kg/m2
STANDARD_DEVIATION 3.890 • n=5 Participants
|
32.06 kg/m2
STANDARD_DEVIATION 3.887 • n=7 Participants
|
31.87 kg/m2
STANDARD_DEVIATION 3.882 • n=5 Participants
|
|
Glycosylated hemoglobin A1c (HbA1c)
|
7.16 Percent
STANDARD_DEVIATION 0.531 • n=5 Participants
|
7.19 Percent
STANDARD_DEVIATION 0.443 • n=7 Participants
|
7.17 Percent
STANDARD_DEVIATION 0.489 • n=5 Participants
|
|
Fasting Plasma Glucose
|
149.60 Milligram per deciliter
STANDARD_DEVIATION 25.086 • n=5 Participants
|
148.01 Milligram per deciliter
STANDARD_DEVIATION 24.650 • n=7 Participants
|
148.82 Milligram per deciliter
STANDARD_DEVIATION 24.815 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values
To evaluate the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin on total body weight after 24 weeks of oral administration of double-blind treatment.
Outcome measures
| Measure |
Placebo Plus Metformin
n=91 Participants
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=89 Participants
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Adjusted Mean Change in Total Body Weight
|
-0.88 kg
95% Confidence Interval 0.2746 • Interval -1.43 to -0.34
|
-2.96 kg
95% Confidence Interval 0.2766 • Interval -3.51 to -2.41
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on waist circumference.
Outcome measures
| Measure |
Placebo Plus Metformin
n=91 Participants
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=89 Participants
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Adjusted Mean Change in Waist Circumference
|
-0.99 cm
95% Confidence Interval 0.4349 • Interval -1.84 to -0.13
|
-2.51 cm
95% Confidence Interval 0.4388 • Interval -3.38 to -1.64
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on total body fat mass measured by dual energy X-ray absorptiometry.
Outcome measures
| Measure |
Placebo Plus Metformin
n=79 Participants
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=82 Participants
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Adjusted Mean Change in Body Fat Mass
|
-0.74 kg
95% Confidence Interval 0.2670 • Interval -1.27 to -0.22
|
-2.22 kg
95% Confidence Interval 0.2626 • Interval -2.74 to -1.7
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on body weight decrease ≥5%. Least Squares Mean represents the percent of participants adjusted for body weight baseline value.
Outcome measures
| Measure |
Placebo Plus Metformin
n=91 Participants
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=89 Participants
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Proportion of Participants With Body Weight Decrease ≥5%
|
4.3 Percentage of participants
Interval 0.1 to 8.6
|
30.6 Percentage of participants
Interval 21.1 to 40.2
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 102Population: Safety Analysis Set (all participants who received at least one dose of double-blind study medication)
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at lumbar spine (L1-4) as measured by Dual Energy X-ray Absorptiometry.
Outcome measures
| Measure |
Placebo Plus Metformin
n=71 Participants
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=68 Participants
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Adjusted Percent Change in Bone Mineral Density (BMD) at Lumbar Spine (L1-4)
|
0.47 Percent
Interval -0.32 to 1.27
|
0.69 Percent
Interval -0.19 to 1.57
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 102Population: Safety Analysis Set (all participants who received at least one dose of double-blind study medication)
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at femoral neck as measured by Dual Energy X-ray Absorptiometry.
Outcome measures
| Measure |
Placebo Plus Metformin
n=71 Participants
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=68 Participants
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Adjusted Percent Change in Bone Mineral Density (BMD) at Femoral Neck
|
0.09 Percent
Interval -0.83 to 1.01
|
-0.85 Percent
Interval -1.85 to 0.16
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 102Population: Safety Analysis Set (all participants who received at least one dose of double-blind study medication)
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at total hip as measured by Dual Energy X-ray Absorptiometry.
Outcome measures
| Measure |
Placebo Plus Metformin
n=71 Participants
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=68 Participants
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Adjusted Percent Change in Bone Mineral Density (BMD) at Total Hip
|
-0.37 Percent
Interval -1.0 to 0.26
|
-0.82 Percent
Interval -1.52 to -0.12
|
Adverse Events
Placebo Plus Metformin
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Dapagliflozin Plus Metformin
Serious events: 6 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo Plus Metformin
n=91 participants at risk
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=91 participants at risk
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/91 • 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 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.
|
2.2%
2/91 • 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 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.
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/91 • 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 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.
|
1.1%
1/91 • 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 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.
|
|
Gastrointestinal disorders
Oesophageal varices hemorrhage
|
0.00%
0/91 • 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 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.
|
1.1%
1/91 • 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 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
Spinal osteoarthritis
|
0.00%
0/91 • 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 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.
|
1.1%
1/91 • 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 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
Transient ischemic attack
|
0.00%
0/91 • 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 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.
|
1.1%
1/91 • 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 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
|
0.00%
0/91 • 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 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.
|
1.1%
1/91 • 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 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.
|
|
Eye disorders
Ulcerative keratitis
|
1.1%
1/91 • 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 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.
|
0.00%
0/91 • 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 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.
|
Other adverse events
| Measure |
Placebo Plus Metformin
n=91 participants at risk
Placebo oral once daily plus metformin over 24 weeks
|
Dapagliflozin Plus Metformin
n=91 participants at risk
Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.5%
5/91 • 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 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%
6/91 • 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 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
|
5.5%
5/91 • 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 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.
|
1.1%
1/91 • 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 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
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