Trial Outcomes & Findings for Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes (NCT NCT02460978)

NCT ID: NCT02460978

Last Updated: 2019-03-05

Results Overview

To compare the change from baseline in HbA1c between dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 815 participants
• Primary outcome timeframe: Baseline and 24 weeks
• Results posted on: 2019-03-05

Participant Flow

The results on this form are from the 24 week short-term double-blind treatment period. This study was conducted at 148 centers in 13 countries from 8 July 2015 to 2 Sep 2017.

815 participants were randomized. Of the 195 participants not randomized: 97 No longer met study criteria, 44 withdrew consent, 13 were lost to follow-up, and 41 did not continue for other reasons. Two participants did not receive any study drug and were excluded from analyses. Thus, the total number of subjects is 813.

Participant milestones

Measure	DAPA 5 MG + INS Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS Dapagliflozin 10 mg plus insulin	PLA + INS Placebo plus insulin
Overall Study STARTED	271	270	272
Overall Study COMPLETED	244	245	239
Overall Study NOT COMPLETED	27	25	33

Reasons for withdrawal

Measure	DAPA 5 MG + INS Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS Dapagliflozin 10 mg plus insulin	PLA + INS Placebo plus insulin
Overall Study Adverse Event	17	11	11
Overall Study Withdrawal by Subject	5	5	14
Overall Study Lost to Follow-up	2	3	1
Overall Study Protocol Violation	1	1	1
Overall Study Discontinued due to DKA/hypoglycemia	2	5	4
Overall Study Pregnancy	0	0	2

Baseline Characteristics

Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes

Baseline characteristics by cohort

Measure	DAPA 5 MG + INS n=271 Participants Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=270 Participants Dapagliflozin 10 mg plus insulin	PLA + INS n=272 Participants Placebo plus insulin	Total n=813 Participants Total of all reporting groups
Age, Continuous	42.7 Years STANDARD_DEVIATION 13.35 • n=5 Participants	42.4 Years STANDARD_DEVIATION 12.80 • n=7 Participants	43.0 Years STANDARD_DEVIATION 13.73 • n=5 Participants	42.7 Years STANDARD_DEVIATION 13.29 • n=4 Participants
Sex: Female, Male Female	153 Participants n=5 Participants	149 Participants n=7 Participants	153 Participants n=5 Participants	455 Participants n=4 Participants
Sex: Female, Male Male	118 Participants n=5 Participants	121 Participants n=7 Participants	119 Participants n=5 Participants	358 Participants n=4 Participants
Race/Ethnicity, Customized White	210 Participants n=5 Participants	219 Participants n=7 Participants	208 Participants n=5 Participants	637 Participants n=4 Participants
Race/Ethnicity, Customized Black or African-American	4 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized Asian	57 Participants n=5 Participants	44 Participants n=7 Participants	59 Participants n=5 Participants	160 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: The analysis population for this endpoint is the number of subjects in the full analysis set with non-missing baseline and at least one post-baseline value. The full analysis set consists of all randomized subjects who took at least one dose of double-blind study medication during the short-term double-blind period.

To compare the change from baseline in HbA1c between dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment

Outcome measures

Measure	DAPA 5 MG + INS n=266 Participants Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=267 Participants Dapagliflozin 10 mg plus insulin	PLA + INS n=267 Participants Placebo plus insulin
Adjusted Mean Change From Baseline in HbA1c at Week 24	-0.34 HbA1c (%) Interval -0.43 to -0.25	-0.39 HbA1c (%) Interval -0.48 to -0.3	0.03 HbA1c (%) Interval -0.06 to 0.12

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Number of subjects in full analysis set with non-missing baseline and at least one post-baseline value

To compare the percent change from baseline in total daily insulin dose with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment

Outcome measures

Measure	DAPA 5 MG + INS n=270 Participants Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=267 Participants Dapagliflozin 10 mg plus insulin	PLA + INS n=266 Participants Placebo plus insulin
Adjusted Mean Percentage Change From Baseline in Total Daily Insulin Dose at Week 24	-8.73 Percentage change Interval -11.09 to -6.31	-9.05 Percentage change Interval -11.43 to -6.6	2.29 Percentage change Interval -0.41 to 5.06

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Number of subjects in full analysis set with non-missing baseline and at least one post-baseline value

To compare the percentage change from baseline in body weight with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment

Outcome measures

Measure	DAPA 5 MG + INS n=269 Participants Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=269 Participants Dapagliflozin 10 mg plus insulin	PLA + INS n=272 Participants Placebo plus insulin
Adjusted Mean Percentage Change From Baseline in Body Weight at Week 24	-3.22 Percentage change Interval -3.76 to -2.69	-3.76 Percentage change Interval -4.29 to -3.22	-0.02 Percentage change Interval -0.57 to 0.54

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: The number of subjects in the full analysis set with non-missing baseline and at least one post-baseline value

To compare the change from baseline in mean value of 24-hour glucose readings obtained from CGM with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment

Outcome measures

Measure	DAPA 5 MG + INS n=252 Participants Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=255 Participants Dapagliflozin 10 mg plus insulin	PLA + INS n=257 Participants Placebo plus insulin
Adjusted Mean Change From Baseline in 24-hour Continuous Glucose Monitoring (CGM) Mean Value at Week 24	-6.46 mg/dL Interval -10.04 to -2.87	-10.54 mg/dL Interval -14.14 to -6.94	9.20 mg/dL Interval 5.57 to 12.83

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Number of subjects in the full analysis set with non-missing baseline and at least one post-baseline value

To compare the change from baseline in mean amplitude of glucose excursions (MAGE) of 24-hour glucose readings obtained from CGM with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment

Outcome measures

Measure	DAPA 5 MG + INS n=252 Participants Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=255 Participants Dapagliflozin 10 mg plus insulin	PLA + INS n=257 Participants Placebo plus insulin
Adjusted Mean Change From Baseline in 24-hour CGM Mean Amplitude of Glycemic Excursion (MAGE) Value at Week 24	-10.17 mg/dL Interval -13.9 to -6.45	-9.68 mg/dL Interval -13.44 to -5.93	-0.33 mg/dL Interval -4.12 to 3.46

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Number of subjects in the full analysis set with non-missing baseline and at least one post-baseline value

To compare the change from baseline in the percent of 24-hour glucose readings obtained from CGM that falls within the target range of >70 mg/dL and <=180 mg/dL with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment

Outcome measures

Measure	DAPA 5 MG + INS n=252 Participants Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=255 Participants Dapagliflozin 10 mg plus insulin	PLA + INS n=257 Participants Placebo plus insulin
Change From Baseline in the Percent of 24-hour Glucose Readings Obtained From CGM That Falls Within the Target Range of > 70 mg/dL and <= 180 mg/dL (%) at Week 24	5.92 % of readings Interval 4.32 to 7.52	7.60 % of readings Interval 5.98 to 9.21	-3.10 % of readings Interval -4.73 to -1.47

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Number of subjects in the full analysis set with non-missing baseline and Week 24 (LOCF) values.

To compare dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin for the proportion of subjects achieving an HbA1c reduction from baseline to Week 24 visit >=0.5% without severe hypoglycemia events

Outcome measures

Measure	DAPA 5 MG + INS n=266 Participants Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=267 Participants Dapagliflozin 10 mg plus insulin	PLA + INS n=269 Participants Placebo plus insulin
Percentage of Subjects With HbA1c Reduction From Baseline to Week 24 Last Observation Carried Forward (LOCF) >= 0.5% and Without Severe Hypoglycemia Events at Week 24 Number of Responders	105 Participants	111 Participants	54 Participants

Adverse Events

DAPA 5 MG + INS

Serious events: 18 serious events

Other events: 79 other events

Deaths: 0 deaths

DAPA 10 MG + INS

Serious events: 7 serious events

Other events: 77 other events

Deaths: 0 deaths

PLA + INS

Serious events: 5 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Measure	DAPA 5 MG + INS n=271 participants at risk Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=270 participants at risk Dapagliflozin 10 mg plus insulin	PLA + INS n=272 participants at risk Placebo plus insulin
Metabolism and nutrition disorders Diabetic ketoacidosis	2.6% 7/271 • Number of events 7 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	1.1% 3/270 • Number of events 3 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Metabolism and nutrition disorders Hypoglycemia	1.1% 3/271 • Number of events 4 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/272 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Metabolism and nutrition disorders Ketoacidosis	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Metabolism and nutrition disorders Ketosis	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Metabolism and nutrition disorders Lactic acidosis	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/272 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Nervous system disorders Cerebral haemorrhage	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Nervous system disorders Coma	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Nervous system disorders Diabetic hyperglycaemic coma	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Nervous system disorders Seizure	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Nervous system disorders Cerebral infarction	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Nervous system disorders Cerebrovascular accident	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/272 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Nervous system disorders Hypoglycaemic coma	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Nervous system disorders Hypoglycaemic seizure	0.74% 2/271 • Number of events 2 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Injury, poisoning and procedural complications Femur fracture	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Injury, poisoning and procedural complications Subarachnoid haemorrhage	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Injury, poisoning and procedural complications Foot fracture	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Cardiac disorders Cardiac arrest	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Cardiac disorders Angina pectoris	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/272 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Gastrointestinal disorders Enteritis	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
General disorders Chest pain	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/270 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Infections and infestations Cellulitis	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Infections and infestations Labyrinthitis	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Infections and infestations Pneumonia	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Infections and infestations Pyelonephritis	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Infections and infestations Sepsis	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Infections and infestations Urinary tract infection	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/271 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/272 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Renal and urinary disorders Acute prerenal failure	0.37% 1/271 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/270 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.00% 0/272 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).

Other adverse events

Measure	DAPA 5 MG + INS n=271 participants at risk Dapagliflozin 5 mg plus insulin	DAPA 10 MG + INS n=270 participants at risk Dapagliflozin 10 mg plus insulin	PLA + INS n=272 participants at risk Placebo plus insulin
Infections and infestations Viral upper respiratory tract infection	14.4% 39/271 • Number of events 46 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	16.3% 44/270 • Number of events 56 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	15.4% 42/272 • Number of events 51 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Nervous system disorders Headache	3.7% 10/271 • Number of events 11 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	5.6% 15/270 • Number of events 15 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	3.7% 10/272 • Number of events 11 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Renal and urinary disorders Pollakiuria	8.1% 22/271 • Number of events 23 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	5.2% 14/270 • Number of events 15 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	2.2% 6/272 • Number of events 6 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
General disorders Thirst	2.2% 6/271 • Number of events 7 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	5.2% 14/270 • Number of events 14 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	0.37% 1/272 • Number of events 1 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).
Infections and infestations Upper respiratory tract infection	5.9% 16/271 • Number of events 21 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	4.4% 12/270 • Number of events 12 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).	4.4% 12/272 • Number of events 12 • All adverse events (AEs), including serious adverse events (SAEs), were collected from the time informed consent was signed throughout the treatment period (through week 24).

Additional Information

Anna Maria Langkilde

AstraZeneca

Phone: +46 31 7761000

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