Trial Outcomes & Findings for A Trial Comparing the Safety and Efficacy of Insulin Degludec and Insulin Glargine, With or Without OADs in Subjects With Type 2 Diabetes (NCT NCT02030600)

NCT ID: NCT02030600

Last Updated: 2019-05-10

Results Overview

Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of \<56 mg/dL (3.1 mmol/L), with symptoms consistent with hypoglycaemia. Treatment emergent hypoglycaemic episode was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

721 participants

Primary outcome timeframe

After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)

Results posted on

2019-05-10

Participant Flow

The trial was conducted at 152 sites in the United States.

Participant milestones

Participant milestones
Measure	Insulin Degludec/Insulin Glargine (IDeg/IGlar) Subjects received insulin degludec (IDeg) in treatment period 1 and insulin glargine (IGlar) in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg and IGlar were administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Doses of IDeg and IGlar were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting self-measured plasma glucose (SMPG) values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine/Insulin Degludec (IGlar/IDeg) Subjects received IGlar in treatment period 1 and IDeg in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar and IDeg were administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total insulin daily dose was recommended. Doses of IGlar and IDeg were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Treatment Period 1 STARTED	361	360
Treatment Period 1 Exposed	356	357
Treatment Period 1 COMPLETED	308	315
Treatment Period 1 NOT COMPLETED	53	45
Treatment Period 2 STARTED	308	315
Treatment Period 2 COMPLETED	283	297
Treatment Period 2 NOT COMPLETED	25	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Degludec/Insulin Glargine (IDeg/IGlar) Subjects received insulin degludec (IDeg) in treatment period 1 and insulin glargine (IGlar) in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg and IGlar were administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Doses of IDeg and IGlar were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting self-measured plasma glucose (SMPG) values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine/Insulin Degludec (IGlar/IDeg) Subjects received IGlar in treatment period 1 and IDeg in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar and IDeg were administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total insulin daily dose was recommended. Doses of IGlar and IDeg were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Treatment Period 1 Adverse Event	5	7
Treatment Period 1 Lack of Efficacy	0	1
Treatment Period 1 Lost to Follow-up	11	3
Treatment Period 1 Protocol Violation	22	17
Treatment Period 1 Withdrawal by Subject	13	17
Treatment Period 1 Casebook Unsigned	1	0
Treatment Period 1 Unclassified	1	0
Treatment Period 2 Adverse Event	4	4
Treatment Period 2 Lack of Efficacy	2	1
Treatment Period 2 Lost to Follow-up	4	2
Treatment Period 2 Protocol Violation	1	2
Treatment Period 2 Withdrawal by Subject	13	9
Treatment Period 2 Unclassified	1	0

Baseline Characteristics

A Trial Comparing the Safety and Efficacy of Insulin Degludec and Insulin Glargine, With or Without OADs in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Degludec/Insulin Glargine (IDeg/IGlar) n=360 Participants Subjects received IDeg in treatment period 1 and IGlar in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg and IGlar were administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Doses of IDeg and IGlar were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine/Insulin Degludec (IGlar/IDeg) n=360 Participants Subjects received IGlar in treatment period 1 and IDeg in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar and IDeg were administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total insulin daily dose was recommended. Doses of IGlar and IDeg were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Total n=720 Participants Total of all reporting groups
Age, Continuous	61.5 years STANDARD_DEVIATION 10.7 • n=5 Participants	61.2 years STANDARD_DEVIATION 10.3 • n=7 Participants	61.4 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	169 Participants n=5 Participants	169 Participants n=7 Participants	338 Participants n=5 Participants
Sex: Female, Male Male	191 Participants n=5 Participants	191 Participants n=7 Participants	382 Participants n=5 Participants
Glycosylated haemoglobin	7.6 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1 • n=5 Participants	7.6 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1 • n=7 Participants	7.6 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1 • n=5 Participants
Fasting plasma glucose	139.2 mg/dL STANDARD_DEVIATION 53.5 • n=5 Participants	134.9 mg/dL STANDARD_DEVIATION 51.6 • n=7 Participants	137.0 mg/dL STANDARD_DEVIATION 52.6 • n=5 Participants

PRIMARY outcome

Timeframe: After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)

Population: The trial followed a cross over design. Descriptive analysis was based on the safety analysis set (subjects receiving at least one dose of the investigational product or its comparator). Number of subjects analysed=subjects with available data for the endpoint as per individual trial products. Statistical analysis was performed on full analysis set

Outcome measures

Outcome measures
Measure	Insulin Degludec (IDeg) n=632 Participants Subjects receiving IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine (IGlar) n=618 Participants Subjects receiving IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Maintenance Period	353 events	496 events

SECONDARY outcome

Timeframe: After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)

Severe or BG confirmed symptomatic nocturnal hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of \<56 mg/dL (3.1 mmol/L), with symptoms consistent with hypoglycaemia and with time of onset between 00:01 and 05.59 a.m., both inclusive. Treatment emergent hypoglycaemic episode was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec (IDeg) n=632 Participants Subjects receiving IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine (IGlar) n=618 Participants Subjects receiving IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Nocturnal Hypoglycaemic Episode During the Maintenance Period	105 events	175 events

SECONDARY outcome

Timeframe: After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)

Population: The trial followed a cross over design. Descriptive analysis was based on the safety analysis set. Number of subjects analysed=subjects with available data for the endpoint as per individual trial products. Statistical analysis was performed on subjects in full analysis set with exposure in both maintenance periods.

Percentage of subjects who experienced one or more severe hypoglycaemic episodes during the maintenance period. Severe hypoglycaemia (according to the American Diabetes Association 2013 definition): A hypoglycaemic episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose values may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.

Outcome measures

Outcome measures
Measure	Insulin Degludec (IDeg) n=632 Participants Subjects receiving IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine (IGlar) n=618 Participants Subjects receiving IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Proportion of Subjects With One or More Severe Hypoglycaemic Episodes During the Maintenance Period	1.6 percentage of subjects	2.4 percentage of subjects

SECONDARY outcome

Timeframe: During 32 weeks of treatment for each treatment period

Population: Safety analysis set included all subjects receiving at least one dose of the investigational product or its comparator (Total number of subjects analysed for this endpoint: 713).

Treatment emergent adverse event was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec (IDeg) n=671 Participants Subjects receiving IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine (IGlar) n=665 Participants Subjects receiving IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Incidence of Treatment Emergent Adverse Events	1293 events	1381 events

SECONDARY outcome

Timeframe: Week 32, Week 64

Population: Full analysis set. Here, 'n' specifies the number of subjects with available data at specified timepoint.

Change from baseline in HbA1c (glycosylated haemoglobin) at week 32 (treatment period 1) and at week 64 (treatment period 2). Week 32 HbA1c value was considered as baseline for calculating change from baseline in HbA1c at week 64.

Outcome measures

Outcome measures
Measure	Insulin Degludec (IDeg) n=360 Participants Subjects receiving IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine (IGlar) n=360 Participants Subjects receiving IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Change From Baseline in HbA1c (Glycosylated Haemoglobin) week 64 (n=295, 301)	0.03 percentage of glycosylated haemoglobin Standard Deviation 0.75	0.10 percentage of glycosylated haemoglobin Standard Deviation 0.83
Change From Baseline in HbA1c (Glycosylated Haemoglobin) week 32 (n=308, 313)	-0.49 percentage of glycosylated haemoglobin Standard Deviation 0.99	-0.58 percentage of glycosylated haemoglobin Standard Deviation 1.02

SECONDARY outcome

Timeframe: week 32, week 64

Population: Full analysis set. Here, 'n' specifies the number of subjects with available data at specified timepoint.

Fasting plasma glucose values at week 32 and week 64.

Outcome measures

Outcome measures
Measure	Insulin Degludec (IDeg) n=360 Participants Subjects receiving IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine (IGlar) n=360 Participants Subjects receiving IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
FPG (Fasting Plasma Glucose) week 32 (n=307, 311)	107.33 mg/dL Standard Deviation 41.72	106.96 mg/dL Standard Deviation 39.81
FPG (Fasting Plasma Glucose) week 64 (n=293, 302)	114.07 mg/dL Standard Deviation 51.91	107.55 mg/dL Standard Deviation 51.30

Adverse Events

Insulin Degludec (IDeg)

Serious events: 64 serious events

Other events: 93 other events

Deaths: 0 deaths

Insulin Glargine (IGlar)

Serious events: 65 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Insulin Degludec (IDeg) n=671 participants at risk Subjects receiving IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Insulin Glargine (IGlar) n=665 participants at risk Subjects receiving IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Infections and infestations Nasopharyngitis	7.5% 50/671 • Number of events 59 • From the first day of exposure to randomised treatment and no later than the last day of randomised treatment (64 weeks) Subjects in the safety analysis set contributed to the evaluation of adverse events. Treatment emergent adverse event was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.	6.2% 41/665 • Number of events 49 • From the first day of exposure to randomised treatment and no later than the last day of randomised treatment (64 weeks) Subjects in the safety analysis set contributed to the evaluation of adverse events. Treatment emergent adverse event was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.
Infections and infestations Upper respiratory tract infection	6.6% 44/671 • Number of events 53 • From the first day of exposure to randomised treatment and no later than the last day of randomised treatment (64 weeks) Subjects in the safety analysis set contributed to the evaluation of adverse events. Treatment emergent adverse event was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.	5.6% 37/665 • Number of events 44 • From the first day of exposure to randomised treatment and no later than the last day of randomised treatment (64 weeks) Subjects in the safety analysis set contributed to the evaluation of adverse events. Treatment emergent adverse event was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.

Additional Information

Global Clinical Registry (GCR, 1452)

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee At the end of the trial, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.
Publication restrictions are in place

Restriction type: OTHER