Trial Outcomes & Findings for Comparison of NN1250 With Insulin Glargine in Type 1 Diabetes (NCT NCT01079234)

NCT ID: NCT01079234

Last Updated: 2017-02-09

Results Overview

Change from baseline in HbA1c after 26 weeks of treatment

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

493 participants

Primary outcome timeframe

Week 0, Week 26

Results posted on

2017-02-09

Participant Flow

The main/extension trial periods were conducted at 71/68 sites in 6 countries: Belgium (5/5 sites), Germany (7/7 sites), Norway (5/5 sites), Poland (5/5 sites), United Kingdom (UK) (12/11 sites), and United States of America (U.S.) (37/35 sites). 57 patients did not participate in the extension trial.

All subjects who completed the 26-week main trial and were found to be eligible for the extension trial were offered to participate in the 26-week extension trial (NCT01079234). Total duration of trial was up to 52 weeks (26 weeks+ 26 weeks) with two times 7-12 day follow-up periods.

Participant milestones

Participant milestones
Measure	IDeg OD FF Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IDeg OD Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with the evening meal in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.	IDeg OD F The subjects randomised to the 2 insulin degludec (IDeg) treatment arms in the main period (IDeg OD FF and IDeg OD) were pooled into this IDeg OD Free Flex arm (IDeg OD F). IDeg was given once daily (OD) subcutaneously (s.c.) at any time of the day (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in the extension period (52 weeks in total). Insulin doses were individually adjusted by the subjects.
Main: Week 0 to 26 STARTED	164	165	164	0
Main: Week 0 to 26 Exposed	164	165	161	0
Main: Week 0 to 26 COMPLETED	138	139	152	0
Main: Week 0 to 26 NOT COMPLETED	26	26	12	0
Extension: Week 27 to 52 STARTED	0	0	133	239
Extension: Week 27 to 52 COMPLETED	0	0	122	223
Extension: Week 27 to 52 NOT COMPLETED	0	0	11	16

Reasons for withdrawal

Reasons for withdrawal
Measure	IDeg OD FF Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IDeg OD Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with the evening meal in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.	IDeg OD F The subjects randomised to the 2 insulin degludec (IDeg) treatment arms in the main period (IDeg OD FF and IDeg OD) were pooled into this IDeg OD Free Flex arm (IDeg OD F). IDeg was given once daily (OD) subcutaneously (s.c.) at any time of the day (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in the extension period (52 weeks in total). Insulin doses were individually adjusted by the subjects.
Main: Week 0 to 26 Adverse Event	5	4	1	0
Main: Week 0 to 26 Lack of Efficacy	2	1	1	0
Main: Week 0 to 26 Protocol Violation	6	2	4	0
Main: Week 0 to 26 Withdrawal criteria	6	6	2	0
Main: Week 0 to 26 Unclassified	7	13	4	0
Extension: Week 27 to 52 Adverse Event	0	0	1	0
Extension: Week 27 to 52 Lack of Efficacy	0	0	0	2
Extension: Week 27 to 52 Protocol Violation	0	0	2	5
Extension: Week 27 to 52 Withdrawal criteria	0	0	4	2
Extension: Week 27 to 52 Unclassified	0	0	4	7

Baseline Characteristics

Comparison of NN1250 With Insulin Glargine in Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IDeg OD FF n=164 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IDeg OD n=165 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with the evening meal in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IGlar OD n=164 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.	Total n=493 Participants Total of all reporting groups
Age, Continuous	42.6 years STANDARD_DEVIATION 13.4 • n=5 Participants	44.5 years STANDARD_DEVIATION 13.1 • n=7 Participants	44.1 years STANDARD_DEVIATION 12.6 • n=5 Participants	43.7 years STANDARD_DEVIATION 13.1 • n=4 Participants
Gender Female	62 Participants n=5 Participants	71 Participants n=7 Participants	76 Participants n=5 Participants	209 Participants n=4 Participants
Gender Male	102 Participants n=5 Participants	94 Participants n=7 Participants	88 Participants n=5 Participants	284 Participants n=4 Participants
HbA1c (glycosylated haemoglobin)	7.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.0 • n=5 Participants	7.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=7 Participants	7.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants	7.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=4 Participants
Fasting plasma glucose (FPG)	9.6 mmol/L STANDARD_DEVIATION 4.1 • n=5 Participants	10.0 mmol/L STANDARD_DEVIATION 4.0 • n=7 Participants	9.7 mmol/L STANDARD_DEVIATION 4.2 • n=5 Participants	9.8 mmol/L STANDARD_DEVIATION 4.1 • n=4 Participants

PRIMARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF).

Change from baseline in HbA1c after 26 weeks of treatment

Outcome measures

Outcome measures
Measure	IDeg OD FF n=164 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IDeg OD n=165 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with the evening meal in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IGlar OD n=164 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.
Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment	-0.40 percentage of glycosylated haemoglobin Standard Deviation 0.59	-0.41 percentage of glycosylated haemoglobin Standard Deviation 0.71	-0.58 percentage of glycosylated haemoglobin Standard Deviation 0.72

PRIMARY outcome

Timeframe: Week 0 to Week 52 + 7 days follow up

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator. The subjects randomised to 2 IDeg arms during the main trial were pooled into the IDeg OD F in extension trial.

Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

Outcome measures

Outcome measures
Measure	IDeg OD FF n=161 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IDeg OD n=329 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with the evening meal in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.
Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	6341 Episodes/100 years of patient exposure	6811 Episodes/100 years of patient exposure	—

PRIMARY outcome

Timeframe: Week 0 to Week 52 + 7 days follow up

Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.The subjects randomised to 2 IDeg arms during the main trial were pooled into the IDeg OD F in extension trial.

Outcome measures

Outcome measures
Measure	IDeg OD FF n=161 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IDeg OD n=329 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with the evening meal in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.
Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	848 Episodes/100 years of patient exposure	640 Episodes/100 years of patient exposure	—

SECONDARY outcome

Timeframe: Week 0, Week 52

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF). The subjects randomised to 2 IDeg arms during the main trial were pooled into the IDeg OD F in extension trial.

Change from baseline in HbA1c after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	IDeg OD FF n=164 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IDeg OD n=329 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with the evening meal in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.
Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment	-0.21 percentage of glycosylated haemoglobin Standard Deviation 0.73	-0.13 percentage of glycosylated haemoglobin Standard Deviation 0.67	—

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF). For 6 subjects baseline values were missing.

Change from baseline in FPG after 26 weeks of treatment

Outcome measures

Outcome measures
Measure	IDeg OD FF n=161 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IDeg OD n=164 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with the evening meal in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IGlar OD n=162 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.
Main Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 26 Weeks of Treatment	-1.28 mmol/L Standard Deviation 5.03	-2.54 mmol/L Standard Deviation 5.11	-1.33 mmol/L Standard Deviation 5.21

SECONDARY outcome

Timeframe: Week 0, Week 52

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF). FPG baseline values were missing for 6 subjects. The subjects randomised to 2 IDeg arms during the main trial were pooled into the IDeg OD F in extension trial.

Change from baseline in FPG after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	IDeg OD FF n=162 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IDeg OD n=325 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with the evening meal in combination with insulin aspart (IAsp) for 26 weeks in main period. Insulin doses were individually adjusted by the subjects.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.
Extension Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment	-0.61 mmol/L Standard Deviation 5.23	-1.73 mmol/L Standard Deviation 5.32	—

Adverse Events

IDeg OD F

Serious events: 25 serious events

Other events: 187 other events

Deaths: 0 deaths

IGlar OD

Serious events: 12 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	IDeg OD F n=329 participants at risk The subjects randomised to the 2 insulin degludec (IDeg) treatment arms in the main period (IDeg OD FF and IDeg OD) were pooled into this IDeg OD Free Flex arm (IDeg OD F). IDeg was given once daily (OD) subcutaneously (s.c.) at any time of the day (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in the extension period (52 weeks in total). Insulin doses were individually adjusted by the subjects.	IGlar OD n=161 participants at risk Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.
Gastrointestinal disorders Diarrhoea	2.7% 9/329 • Number of events 15 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	7.5% 12/161 • Number of events 15 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Gastrointestinal disorders Nausea	5.5% 18/329 • Number of events 21 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	5.0% 8/161 • Number of events 13 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Gastrointestinal disorders Vomiting	5.5% 18/329 • Number of events 22 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	6.8% 11/161 • Number of events 12 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Gastroenteritis	5.8% 19/329 • Number of events 22 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	3.7% 6/161 • Number of events 6 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Nasopharyngitis	30.1% 99/329 • Number of events 174 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	29.8% 48/161 • Number of events 85 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Sinusitis	7.0% 23/329 • Number of events 28 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	8.1% 13/161 • Number of events 18 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Upper respiratory tract infection	8.5% 28/329 • Number of events 39 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	13.0% 21/161 • Number of events 30 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Wrong drug administered	5.5% 18/329 • Number of events 19 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	4.3% 7/161 • Number of events 8 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemia	7.3% 24/329 • Number of events 38 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	8.1% 13/161 • Number of events 42 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Headache	10.0% 33/329 • Number of events 61 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	14.9% 24/161 • Number of events 48 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Cough	5.2% 17/329 • Number of events 20 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	6.8% 11/161 • Number of events 13 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.5% 28/329 • Number of events 36 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	8.7% 14/161 • Number of events 15 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Gastroenteritis viral	2.7% 9/329 • Number of events 11 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	6.2% 10/161 • Number of events 14 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.
Publication restrictions are in place

Restriction type: OTHER

Measure	IDeg OD F n=329 participants at risk The subjects randomised to the 2 insulin degludec (IDeg) treatment arms in the main period (IDeg OD FF and IDeg OD) were pooled into this IDeg OD Free Flex arm (IDeg OD F). IDeg was given once daily (OD) subcutaneously (s.c.) at any time of the day (approximately 8-40 hours intervals) in combination with insulin aspart (IAsp) for 26 weeks in the extension period (52 weeks in total). Insulin doses were individually adjusted by the subjects.	IGlar OD n=161 participants at risk Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling in combination with insulin aspart (IAsp) for 52 weeks (26 weeks in main period + 26 weeks in extension period). Insulin doses were individually adjusted by the subjects.
Musculoskeletal and connective tissue disorders Foot deformity	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Eye disorders Retinal haemorrhage	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Abscess limb	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Pyelonephritis	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Incorrect dose administered	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/329 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.62% 1/161 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.61% 2/329 • Number of events 2 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemia	2.4% 8/329 • Number of events 12 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	2.5% 4/161 • Number of events 4 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemic seizure	0.00% 0/329 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.62% 1/161 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemic unconsciousness	1.5% 5/329 • Number of events 5 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	2.5% 4/161 • Number of events 4 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/329 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.62% 1/161 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Hypoglycaemic coma	0.61% 2/329 • Number of events 2 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Transient global amnesia	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Transient ischaemic attack	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Psychiatric disorders Completed suicide	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Cardiac disorders Acute myocardial infarction	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Gastrointestinal disorders Gastritis alcoholic	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Abdominal infection	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Cellulitis	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/329 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.62% 1/161 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications In-stent arterial restenosis	0.00% 0/329 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.62% 1/161 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Vascular pseudo aneurysm	0.00% 0/329 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.62% 1/161 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Wrong drug administered	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hyper osmolar state	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypovolaemia	0.30% 1/329 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/161 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.