Trial Outcomes & Findings for Evaluate Safety as Mono or Combination Therapies With Anti-diabetes Mellitus Drugs in Japanese Subjects With Type 2 Diabetes Mellitus (NCT NCT01294436)

NCT ID: NCT01294436

Last Updated: 2013-12-17

Results Overview

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to adverse events

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 728 participants
• Primary outcome timeframe: Long-term treatment up to 52 weeks
• Results posted on: 2013-12-17

Participant Flow

First subject enrolled: 28-Feb-2011; Last subject last visit: 15-Sep-2012; 1030 participants were enrolled in 56 Japanese centers. 728 Japanese men and women aged >=20 years with inadequate glycemic control (HbA1c levels of 6.5% to 10.0% prior to study treatment) with diet and exercise were treated.

A 6-week wash-out period was applicable only for subjects with ongoing anti-diabetic treatment at enrolment. A 4-week lead-in period was applicable for all subjects.

Participant milestones

Measure	Monotherapy Dapagliflozin 5/10 mg only	All Combination Therapies Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Overall Study STARTED	249	479
Overall Study COMPLETED	221	409
Overall Study NOT COMPLETED	28	70

Reasons for withdrawal

Measure	Monotherapy Dapagliflozin 5/10 mg only	All Combination Therapies Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Overall Study Adverse Event	10	17
Overall Study Withdrawal by Subject	11	28
Overall Study subject no longer meets study criteria	5	20
Overall Study poor/non-compliance	2	5

Baseline Characteristics

Evaluate Safety as Mono or Combination Therapies With Anti-diabetes Mellitus Drugs in Japanese Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Monotherapy n=249 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=479 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs	Total n=728 Participants Total of all reporting groups
Age, Continuous	58.1 years STANDARD_DEVIATION 10.40 • n=5 Participants	57.2 years STANDARD_DEVIATION 10.06 • n=7 Participants	57.5 years STANDARD_DEVIATION 10.18 • n=5 Participants
Age, Customized < 65 years	182 participants n=5 Participants	365 participants n=7 Participants	547 participants n=5 Participants
Age, Customized 65 - <75 years	55 participants n=5 Participants	102 participants n=7 Participants	157 participants n=5 Participants
Age, Customized >= 75 years	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants
Sex: Female, Male Female	103 Participants n=5 Participants	211 Participants n=7 Participants	314 Participants n=5 Participants
Sex: Female, Male Male	146 Participants n=5 Participants	268 Participants n=7 Participants	414 Participants n=5 Participants
Region of Enrollment Japan	249 participants n=5 Participants	479 participants n=7 Participants	728 participants n=5 Participants
Body Weight	67.77 kg STANDARD_DEVIATION 13.437 • n=5 Participants	67.40 kg STANDARD_DEVIATION 14.529 • n=7 Participants	67.52 kg STANDARD_DEVIATION 14.157 • n=5 Participants
Body Mass Index	25.72 kg/m^2 STANDARD_DEVIATION 4.196 • n=5 Participants	25.61 kg/m^2 STANDARD_DEVIATION 4.440 • n=7 Participants	25.64 kg/m^2 STANDARD_DEVIATION 4.355 • n=5 Participants
Seated Systolic Blood Pressure	127.5 mmHg STANDARD_DEVIATION 13.73 • n=5 Participants	125.8 mmHg STANDARD_DEVIATION 14.13 • n=7 Participants	126.4 mmHg STANDARD_DEVIATION 14.01 • n=5 Participants
HbA1c	7.53 Percent STANDARD_DEVIATION 0.761 • n=5 Participants	7.82 Percent STANDARD_DEVIATION 0.865 • n=7 Participants	7.72 Percent STANDARD_DEVIATION 0.842 • n=5 Participants
Fasting Plasma Glucose (FPG)	140.29 mg/dL STANDARD_DEVIATION 25.355 • n=5 Participants	147.35 mg/dL STANDARD_DEVIATION 29.097 • n=7 Participants	144.93 mg/dL STANDARD_DEVIATION 28.057 • n=5 Participants

PRIMARY outcome

Timeframe: Long-term treatment up to 52 weeks

Population: Safety Analysis Set

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to adverse events

Outcome measures

Measure	Monotherapy n=249 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=479 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Proportion of Participants With Adverse Events	79.1 Percentage of participants	72.4 Percentage of participants

PRIMARY outcome

Timeframe: Long-term treatment up to 52 weeks

Population: Safety Analysis Set

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to serious adverse events

Outcome measures

Measure	Monotherapy n=249 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=479 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Proportion of Participants With Serious Adverse Events	5.6 Percentage of participants	3.1 Percentage of participants

PRIMARY outcome

Timeframe: Long-term treatment up to 52 weeks

Population: Safety Analysis Set

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to occurrence of hypoglycemia

Outcome measures

Measure	Monotherapy n=249 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=479 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Proportion of Participants With At Least One Episode of Hypoglycemia	2.4 Percentage of participants	4.0 Percentage of participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Analysis Set, participants with non-missing baseline and week 52 values

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in hematocrit

Outcome measures

Measure	Monotherapy n=220 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=407 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Hematocrit	2.17 Percent Standard Error 0.1396	2.00 Percent Standard Error 0.1115

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Analysis Set, participants with non-missing baseline and week 52 values

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in alanine aminotransferase

Outcome measures

Measure	Monotherapy n=220 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=407 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Alanine Aminotransferase (ALT)	-7.1 U/L Standard Error 0.955	-5.4 U/L Standard Error 0.622

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Analysis Set, participants with non-missing baseline and week 52 values

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in aspartate aminotransferase

Outcome measures

Measure	Monotherapy n=220 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=405 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Aspartate Aminotransferase (AST)	-3.9 U/L Standard Error 0.695	-2.6 U/L Standard Error 0.410

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Analysis Set, participants with non-missing baseline and week 52 values

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood urea nitrogen

Outcome measures

Measure	Monotherapy n=220 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=407 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Blood Urea Nitrogen (BUN)	2.4 mg/dL Standard Error 0.250	2.3 mg/dL Standard Error 0.168

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Analysis Set, participants with non-missing baseline and week 52 values

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in magnesium (1 mEq/L equivalent to 0.50 mmol/L)

Outcome measures

Measure	Monotherapy n=220 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=407 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Magnesium	0.05 mEq/L Standard Error 0.0074	0.05 mEq/L Standard Error 0.0064

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Analysis Set, participants with non-missing baseline and week 52 values

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in serum uric acid

Outcome measures

Measure	Monotherapy n=220 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=407 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Serum Uric Acid	-0.61 mg/dL Standard Error 0.0578	-0.50 mg/dL Standard Error 0.0374

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Analysis Set, participants with non-missing baseline and week 52 values

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in pulse

Outcome measures

Measure	Monotherapy n=220 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=407 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Seated Heart Rate	-0.4 beats per minute (bpm) Standard Deviation 7.52	0.2 beats per minute (bpm) Standard Deviation 7.95

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Analysis Set, participants with non-missing baseline and week 52 values

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure

Outcome measures

Measure	Monotherapy n=220 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=407 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Seated Diastolic Blood Pressure	-2.9 mmHg Standard Deviation 8.16	-2.1 mmHg Standard Deviation 8.73

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Analysis Set, participants with non-missing baseline and week 52 values

To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure

Outcome measures

Measure	Monotherapy n=220 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=407 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Seated Systolic Blood Pressure	-5.2 mmHg Standard Deviation 11.68	-3.9 mmHg Standard Deviation 13.03

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 52

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

To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in HbA1c

Outcome measures

Measure	Monotherapy n=249 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=477 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in HbA1c Levels	-0.66 Percent 95% Confidence Interval 11.68 • Interval -0.75 to -0.57	-0.68 Percent 95% Confidence Interval 13.03 • Interval -0.75 to -0.62

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 52

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

To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in body weight

Outcome measures

Measure	Monotherapy n=249 Participants Dapagliflozin 5/10 mg only	All Combination Therapies n=477 Participants Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Mean Change in Body Weight	-2.58 kg 95% Confidence Interval 11.68 • Interval -2.87 to -2.3	-2.06 kg 95% Confidence Interval 13.03 • Interval -2.31 to -1.81

Adverse Events

Monotherapy

Serious events: 14 serious events

Other events: 71 other events

Deaths: 0 deaths

All Combination Therapies

Serious events: 15 serious events

Other events: 126 other events

Deaths: 0 deaths

Serious adverse events

Measure	Monotherapy n=249 participants at risk Dapagliflozin 5/10 mg only	All Combination Therapies n=479 participants at risk Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Eye disorders AGE RELATED MACULAR DEGENERATION	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 CATARACT	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 RETINAL DETACHMENT	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) COLON CANCER	0.80% 2/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) RECTAL CANCER	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 COLONIC POLYP	0.80% 2/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 GASTROINTESTINAL INFLAMMATION	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 HAEMORRHOIDS	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 CHRONIC SINUSITIS	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 DIVERTICULITIS	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 GASTROENTERITIS	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 LOBAR PNEUMONIA	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 PHARYNGITIS	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 BRAIN STEM HAEMORRHAGE	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 CEREBRAL INFARCTION	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.63% 3/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Injury, poisoning and procedural complications LIMB TRAUMATIC AMPUTATION	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Injury, poisoning and procedural complications SPINAL COMPRESSION FRACTURE	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 OSTEOARTHRITIS	0.40% 1/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 0/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Cardiac disorders TACHYCARDIA PAROXYSMAL	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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 POSITIONAL	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Hepatobiliary disorders CHOLELITHIASIS	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Investigations ELECTROCARDIOGRAM ABNORMAL	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Renal and urinary disorders CALCULUS URINARY	0.00% 0/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	0.21% 1/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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	Monotherapy n=249 participants at risk Dapagliflozin 5/10 mg only	All Combination Therapies n=479 participants at risk Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Infections and infestations NASOPHARYNGITIS	25.3% 63/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.	24.2% 116/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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.
Renal and urinary disorders POLLAKIURIA	5.2% 13/249 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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% 13/479 • Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit 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: ClinicalTrialTransparency@astrazeneca.com

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