Trial Outcomes & Findings for The Safety and Efficacy of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM (NCT NCT02582814)

NCT ID: NCT02582814

Last Updated: 2019-04-12

Results Overview

To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 151 participants
• Primary outcome timeframe: From baseline to 52 weeks
• Results posted on: 2019-04-12

Participant Flow

Participant milestones

Measure	Dapagliflozin 5mg + Insulin dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin dapagliflozin tablet 10mg + adjustable insulin
Overall Study STARTED	76	75
Overall Study COMPLETED	67	68
Overall Study NOT COMPLETED	9	7

Reasons for withdrawal

Measure	Dapagliflozin 5mg + Insulin dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin dapagliflozin tablet 10mg + adjustable insulin
Overall Study Study-specific withdrawal criteria	1	0
Overall Study Withdrawal by Subject	4	3
Overall Study Adverse Event	4	4

Baseline Characteristics

The Safety and Efficacy of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM

Baseline characteristics by cohort

Measure	Dapagliflozin 5mg + Insulin n=76 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin	Total n=151 Participants Total of all reporting groups
Age, Continuous	47.7 years STANDARD_DEVIATION 12.85 • n=5 Participants	48.9 years STANDARD_DEVIATION 12.93 • n=7 Participants	48.3 years STANDARD_DEVIATION 12.86 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	42 Participants n=7 Participants	75 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	33 Participants n=7 Participants	76 Participants n=5 Participants
Race/Ethnicity, Customized Asian	76 Participants n=5 Participants	75 Participants n=7 Participants	151 Participants n=5 Participants
Body Mass Index	25.28 kg/m2 STANDARD_DEVIATION 3.635 • n=5 Participants	24.66 kg/m2 STANDARD_DEVIATION 2.806 • n=7 Participants	24.97 kg/m2 STANDARD_DEVIATION 3.254 • n=5 Participants
Duration of T1DM	14.60 years STANDARD_DEVIATION 8.420 • n=5 Participants	15.94 years STANDARD_DEVIATION 10.328 • n=7 Participants	15.27 years STANDARD_DEVIATION 9.409 • n=5 Participants
HbA1c	8.43 Percent STANDARD_DEVIATION 0.711 • n=5 Participants	8.40 Percent STANDARD_DEVIATION 0.715 • n=7 Participants	8.42 Percent STANDARD_DEVIATION 0.711 • n=5 Participants
C-peptide < 0.1 ng/mL	63 Participants n=5 Participants	65 Participants n=7 Participants	128 Participants n=5 Participants
C-peptide >= 0.1 ng/mL	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to 52 weeks

To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=76 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
Overall Adverse Event Summary Adverse Events · At least one events	67 Participants	55 Participants
Overall Adverse Event Summary Related Adverse Events · At least one events	23 Participants	22 Participants
Overall Adverse Event Summary SAE · At least one events	7 Participants	3 Participants
Overall Adverse Event Summary AEs leading to discontinuation · At least one events	4 Participants	4 Participants
Overall Adverse Event Summary Death · At least one events	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From baseline to 52 weeks

To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=76 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
Hypoglycemia Any Hypoglycemia Episodes · At least one events	75 Participants	75 Participants
Hypoglycemia Severe Hypoglycemia · At least one events	2 Participants	5 Participants
Hypoglycemia Documented Symptomatic Hypoglycemia · At least one events	67 Participants	73 Participants
Hypoglycemia Asymptomatic Hypoglycemia · At least one events	60 Participants	64 Participants
Hypoglycemia Probable Symptomatic Hypoglycemia · At least one events	13 Participants	14 Participants
Hypoglycemia Relative Hypoglycemia · At least one events	14 Participants	11 Participants

PRIMARY outcome

Timeframe: From baseline to 52 weeks

To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=76 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
Diabetic Ketoacidosis (DKA) Definite DKA · At least one events	2 Participants	1 Participants
Diabetic Ketoacidosis (DKA) Possible DKA · At least one events	1 Participants	0 Participants
Diabetic Ketoacidosis (DKA) Unlikely DKA · At least one events	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From baseline to 52 weeks

Population: Subjects with both non-missing baseline and non-missing Week 52 were included.

To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=76 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
Vital Signs (Heart Rate)	-0.3 bpm Standard Deviation 10.07	0.4 bpm Standard Deviation 8.89

PRIMARY outcome

Timeframe: From baseline to 52 weeks

To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=76 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
ECGs Baseline · NORMAL	65 Participants	67 Participants
ECGs Baseline · ABNORMAL	11 Participants	8 Participants
ECGs Baseline · NOT REPORTED	0 Participants	0 Participants
ECGs Week 52 · NORMAL	69 Participants	67 Participants
ECGs Week 52 · ABNORMAL	5 Participants	8 Participants
ECGs Week 52 · NOT REPORTED	2 Participants	0 Participants

PRIMARY outcome

Timeframe: From baseline to 52 weeks

Population: Subjects with non-missing post-baseilne measurements were included.

To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=76 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality) UACR (> 1800mg/g)	0 Participants	1 Participants
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality) Hematocrit (> 55%)	1 Participants	0 Participants
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality) Hemoglobin (> 18g/dL)	2 Participants	1 Participants
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality) Creatinine (>1.5 x ULN pre Rx)	0 Participants	1 Participants
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality) Creatin kinase (> 5x ULN)	1 Participants	1 Participants
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality) Bicarbonate (<= 13 mEq/L)	1 Participants	0 Participants
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality) P (<=1.8/2.1mg/dL for age<=/>65)	1 Participants	1 Participants

PRIMARY outcome

Timeframe: From baseline to 52 weeks

Population: Subjects with both non-missing baseline and non-missing Week 52 were included.

To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=76 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
Vital Signs (Blood Pressure) Change from baseline in SBP(mmHg) at Week 52	-3.4 mmHg Standard Deviation 11.41	-2.9 mmHg Standard Deviation 12.55
Vital Signs (Blood Pressure) Change from baseline in DBP(mmHg) at Week 52	-0.6 mmHg Standard Deviation 8.21	-1.0 mmHg Standard Deviation 7.89

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=74 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=74 Participants dapagliflozin tablet 10mg + adjustable insulin
Adjusted Change From Baseline in HbA1c Week 24	-0.52 percent Interval -0.66 to -0.38	-0.66 percent Interval -0.8 to -0.53
Adjusted Change From Baseline in HbA1c Week 52	-0.33 percent Interval -0.5 to -0.15	-0.36 percent Interval -0.53 to -0.18

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=73 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=73 Participants dapagliflozin tablet 10mg + adjustable insulin
Adjusted Percent Change From Baseline in Total Daily Insulin Dose Week 24	-15.30 percent change Interval -18.55 to -11.92	-15.14 percent change Interval -18.43 to -11.73
Adjusted Percent Change From Baseline in Total Daily Insulin Dose Week 52	-12.27 percent change Interval -15.92 to -8.46	-13.13 percent change Interval -16.77 to -9.33

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=74 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=74 Participants dapagliflozin tablet 10mg + adjustable insulin
Adjusted Percent Change From Baseline in Body Weight Week 24	-3.88 percent change Interval -4.74 to -3.02	-5.26 percent change Interval -6.11 to -4.41
Adjusted Percent Change From Baseline in Body Weight Week 52	-4.25 percent change Interval -5.29 to -3.21	-5.96 percent change Interval -6.98 to -4.93

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=74 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=74 Participants dapagliflozin tablet 10mg + adjustable insulin
Adjusted Change From Baseline in Glycoalbumin Week 24	-2.26 percent Interval -2.83 to -1.7	-2.63 percent Interval -3.22 to -2.04
Adjusted Change From Baseline in Glycoalbumin Week 52	-1.49 percent Interval -2.18 to -0.77	-1.68 percent Interval -2.41 to -0.96

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=73 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=72 Participants dapagliflozin tablet 10mg + adjustable insulin
Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG Week 24	-9.37 mg/dL Interval -15.8 to -2.94	-15.06 mg/dL Interval -21.62 to -8.51
Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG Week 52	-11.62 mg/dL Interval -18.62 to -4.62	-12.93 mg/dL Interval -19.99 to -5.88

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=73 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=73 Participants dapagliflozin tablet 10mg + adjustable insulin
Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG Week 24	-2.33 mg/dL Interval -11.18 to 6.51	-10.08 mg/dL Interval -19.04 to -1.12
Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG Week 52	-6.40 mg/dL Interval -15.45 to 2.64	-5.24 mg/dL Interval -14.32 to 3.83

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: Subjects with non-missing HbA1c baseline and Week24/52 (LOCF) values were included.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=74 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia Week 24	60.8 percentage of participants Interval 48.8 to 72.0	61.3 percentage of participants Interval 49.4 to 72.4
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia Week 52	51.4 percentage of participants Interval 39.4 to 63.1	41.3 percentage of participants Interval 30.1 to 53.3

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: Subjects with non-missing HbA1c baseline and Week24/52 (LOCF) values were included.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=74 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Week 24	62.2 percentage of participants Interval 50.1 to 73.2	66.7 percentage of participants Interval 54.8 to 77.1
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Week 52	51.4 percentage of participants Interval 39.4 to 63.1	45.3 percentage of participants Interval 33.8 to 57.3

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: Subjects with non-missing HbA1c baseline and Week24/52 (LOCF) values were included.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=74 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 Participants dapagliflozin tablet 10mg + adjustable insulin
Proportion of Subjects Achieving HbA1c < 7.0 Percent Week 24	9.5 percentage of participants Interval 3.9 to 18.5	5.3 percentage of participants Interval 1.5 to 13.1
Proportion of Subjects Achieving HbA1c < 7.0 Percent Week 52	6.8 percentage of participants Interval 2.2 to 15.1	2.7 percentage of participants Interval 0.3 to 9.3

SECONDARY outcome

Timeframe: From baseline to 24/52 weeks

Population: Subjects with baseline SBP \>= 140mmHg and/or baselien DBP \>= 90mmHg were included in analysis.

To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin

Outcome measures

Measure	Dapagliflozin 5mg + Insulin n=19 Participants dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=13 Participants dapagliflozin tablet 10mg + adjustable insulin
Adjusted Change From Baseline in SBP in Subjects With Baseline SBP/DBP >= 140/90 mmHg Week 52	-9.8 mmHg Interval -15.1 to -4.5	-14.2 mmHg Interval -20.7 to -7.6
Adjusted Change From Baseline in SBP in Subjects With Baseline SBP/DBP >= 140/90 mmHg Week 24	-5.8 mmHg Interval -11.2 to -0.3	-12.0 mmHg Interval -19.0 to -5.0

Adverse Events

Dapagliflozin 5mg + Insulin

Serious events: 7 serious events

Other events: 66 other events

Deaths: 0 deaths

Dapagliflozin 10mg + Insulin

Serious events: 3 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dapagliflozin 5mg + Insulin n=76 participants at risk dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 participants at risk dapagliflozin tablet 10mg + adjustable insulin
Eye disorders VITREOUS HAEMORRHAGE	0.00% 0/76 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	1.3% 1/75 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Gastrointestinal disorders COLITIS	0.00% 0/76 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	1.3% 1/75 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Metabolism and nutrition disorders DIABETIC KETOACIDOSIS	2.6% 2/76 • Number of events 2 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	1.3% 1/75 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Nervous system disorders HYPOGLYCAEMIC COMA	0.00% 0/76 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	1.3% 1/75 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Cardiac disorders ATRIAL FIBRILLATION	1.3% 1/76 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	0.00% 0/75 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Hepatobiliary disorders HEPATIC FUNCTION ABNORMAL	1.3% 1/76 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	0.00% 0/75 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Infections and infestations GASTROENTERITIS	1.3% 1/76 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	0.00% 0/75 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	1.3% 1/76 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	0.00% 0/75 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Pregnancy, puerperium and perinatal conditions ABORTION SPONTANEOUS	1.3% 1/76 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	0.00% 0/75 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.

Other adverse events

Measure	Dapagliflozin 5mg + Insulin n=76 participants at risk dapagliflozin tablet 5mg + adjustable insulin	Dapagliflozin 10mg + Insulin n=75 participants at risk dapagliflozin tablet 10mg + adjustable insulin
Infections and infestations NASOPHARYNGITIS	32.9% 25/76 • Number of events 39 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	42.7% 32/75 • Number of events 44 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Infections and infestations PHARYNGITIS	6.6% 5/76 • Number of events 6 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	12.0% 9/75 • Number of events 13 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Infections and infestations GASTROENTERITIS	9.2% 7/76 • Number of events 8 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	10.7% 8/75 • Number of events 10 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Gastrointestinal disorders DENTAL CARIES	0.00% 0/76 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	6.7% 5/75 • Number of events 5 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Skin and subcutaneous tissue disorders ECZEMA	5.3% 4/76 • Number of events 4 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	5.3% 4/75 • Number of events 4 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
General disorders THIRST	5.3% 4/76 • Number of events 4 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	5.3% 4/75 • Number of events 4 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Nervous system disorders HEADACHE	5.3% 4/76 • Number of events 4 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	8.0% 6/75 • Number of events 12 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Renal and urinary disorders POLLAKIURIA	9.2% 7/76 • Number of events 7 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	8.0% 6/75 • Number of events 6 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Metabolism and nutrition disorders KETOSIS	5.3% 4/76 • Number of events 8 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	9.3% 7/75 • Number of events 15 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Infections and infestations BRONCHITIS	2.6% 2/76 • Number of events 5 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	5.3% 4/75 • Number of events 4 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Infections and infestations INFLUENZA	5.3% 4/76 • Number of events 4 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	2.7% 2/75 • Number of events 2 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.
Musculoskeletal and connective tissue disorders BACK PAIN	7.9% 6/76 • Number of events 9 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.	1.3% 1/75 • Number of events 1 • 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days Only hypoglycemia/ DKA reported as a serious adverse event are included.

Additional Information

A clinical pharmacology and long-term safety study

AstraZeneca

Phone: +819039706431

Email: Yu.Shimizuishi@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER