Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02030600
Recruitment Status : Completed
First Posted : January 8, 2014
Results First Posted : January 30, 2017
Last Update Posted : May 10, 2019
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Diabetes
Diabetes Mellitus, Type 2
Interventions Drug: insulin degludec
Drug: insulin glargine
Enrollment 721
Recruitment Details The trial was conducted at 152 sites in the United States.
Pre-assignment Details  
Arm/Group Title Insulin Degludec/Insulin Glargine (IDeg/IGlar) Insulin Glargine/Insulin Degludec (IGlar/IDeg)
Hide Arm/Group Description 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). 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).
Period Title: Treatment Period 1
Started 361 360
Exposed 356 357
Completed 308 315
Not Completed 53 45
Reason Not Completed
Adverse Event             5             7
Lack of Efficacy             0             1
Lost to Follow-up             11             3
Protocol Violation             22             17
Withdrawal by Subject             13             17
Casebook Unsigned             1             0
Unclassified             1             0
Period Title: Treatment Period 2
Started 308 315
Completed 283 297
Not Completed 25 18
Reason Not Completed
Adverse Event             4             4
Lack of Efficacy             2             1
Lost to Follow-up             4             2
Protocol Violation             1             2
Withdrawal by Subject             13             9
Unclassified             1             0
Arm/Group Title Insulin Degludec/Insulin Glargine (IDeg/IGlar) Insulin Glargine/Insulin Degludec (IGlar/IDeg) Total
Hide Arm/Group Description 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). 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 of all reporting groups
Overall Number of Baseline Participants 360 360 720
Hide Baseline Analysis Population Description
Full analysis set included all randomised subjects. One subject was excluded from the analysis due to unsigned casebook.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 360 participants 360 participants 720 participants
61.5  (10.7) 61.2  (10.3) 61.4  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 360 participants 360 participants 720 participants
Female
169
  46.9%
169
  46.9%
338
  46.9%
Male
191
  53.1%
191
  53.1%
382
  53.1%
Glycosylated haemoglobin  
Mean (Standard Deviation)
Unit of measure:  Percentage of glycosylated haemoglobin
Number Analyzed 360 participants 360 participants 720 participants
7.6  (1.1) 7.6  (1.1) 7.6  (1.1)
Fasting plasma glucose   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 360 participants 360 participants 720 participants
139.2  (53.5) 134.9  (51.6) 137.0  (52.6)
[1]
Measure Description: Number of subjects analyzed=355 for IDeg/IGlar arm, 358 for IGlar/IDeg arm and 713 for total.
1.Primary Outcome
Title Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Maintenance Period
Hide Description 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.
Time Frame After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Insulin Degludec (IDeg) Insulin Glargine (IGlar)
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 632 618
Measure Type: Number
Unit of Measure: events
353 496
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Degludec (IDeg), Insulin Glargine (IGlar)
Comments

Stepwise hierarchical testing procedure was applied for confirmatory endpoints:

Step 1: Primary analysis: Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the maintenance period

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.61 to 0.80
Estimation Comments Superiority was considered confirmed if the 95% confidence interval for the rate ratio (IDeg/IGlar) was entirely below 1.0.
2.Secondary Outcome
Title Number of Treatment Emergent Severe or BG Confirmed Symptomatic Nocturnal Hypoglycaemic Episode During the Maintenance Period
Hide Description 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.
Time Frame After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Insulin Degludec (IDeg) Insulin Glargine (IGlar)
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 632 618
Measure Type: Number
Unit of Measure: events
105 175
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Degludec (IDeg), Insulin Glargine (IGlar)
Comments

Stepwise hierarchical testing procedure was applied for confirmatory endpoints:

Step 2: Number of treatment-emergent severe or BG confirmed symptomatic nocturnal hypoglycaemic episodes during the maintenance period.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Poisson
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment ratio
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.46 to 0.74
Estimation Comments Superiority was considered confirmed if the 95% confidence interval for the rate ratio (IDeg/IGlar) was entirely below 1.0.
3.Secondary Outcome
Title Proportion of Subjects With One or More Severe Hypoglycaemic Episodes During the Maintenance Period
Hide Description 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.
Time Frame After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Insulin Degludec (IDeg) Insulin Glargine (IGlar)
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 632 618
Measure Type: Number
Unit of Measure: percentage of subjects
1.6 2.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Degludec (IDeg), Insulin Glargine (IGlar)
Comments

Stepwise hierarchical testing procedure:

Step 3: Proportion of subjects with one or more severe hypoglycaemic episodes in the maintenance period.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3458
Comments Superiority was confirmed if the p-value was less than 0.025.
Method McNemar
Comments [Not Specified]
4.Secondary Outcome
Title Incidence of Treatment Emergent Adverse Events
Hide Description 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.
Time Frame During 32 weeks of treatment for each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Insulin Degludec (IDeg) Insulin Glargine (IGlar)
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 671 665
Measure Type: Number
Unit of Measure: events
1293 1381
5.Secondary Outcome
Title Change From Baseline in HbA1c (Glycosylated Haemoglobin)
Hide Description 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.
Time Frame Week 32, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Here, 'n' specifies the number of subjects with available data at specified timepoint.
Arm/Group Title Insulin Degludec/Insulin Glargine (IDeg/IGlar) Insulin Glargine/Insulin Degludec (IGlar/IDeg)
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 360 360
Mean (Standard Deviation)
Unit of Measure: percentage of glycosylated haemoglobin
week 32 (n=308, 313) -0.49  (0.99) -0.58  (1.02)
week 64 (n=295, 301) 0.03  (0.75) 0.10  (0.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Degludec/Insulin Glargine (IDeg/IGlar), Insulin Glargine/Insulin Degludec (IGlar/IDeg)
Comments Change from baseline in HbA1c at week 32 (treatment period 1). Before the primary endpoint was tested, the secondary supportive efficacy endpoint "Change from baseline in HbA1c after 32 weeks of treatment" was tested for non-inferiority as prerequisite for testing the primary endpoint. Analysis was performed using a mixed model for repeated measurement (MMRM) with treatment, sex, antidiabetic therapy at screening, visit and dosing time as fixed effects, and age and baseline HbA1c as covariates.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority of IDeg against IGlar was considered confirmed if the upper bound of the two-sided 95% confidence interval was below or equal to 0.40%.
Method of Estimation Estimation Parameter Treatment contrast
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.04 to 0.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Degludec/Insulin Glargine (IDeg/IGlar), Insulin Glargine/Insulin Degludec (IGlar/IDeg)
Comments Change from baseline in HbA1c at week 64 (treatment period 2). The baseline values are week 32 values. Before the primary endpoint was tested, the secondary supportive efficacy endpoint "Change from baseline in HbA1c after 32 weeks of treatment" was tested for non-inferiority as prerequisite for testing the primary endpoint. Analysis was performed using a MMRM with treatment, sex, antidiabetic therapy at screening, visit and dosing time as fixed effects, and age and baseline HbA1c as covariates.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was considered confirmed if the upper bound of the two-sided 95% confidence interval was below or equal to 0.40%
Method of Estimation Estimation Parameter Treatment contrast
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.07 to 0.18
Estimation Comments [Not Specified]
6.Secondary Outcome
Title FPG (Fasting Plasma Glucose)
Hide Description Fasting plasma glucose values at week 32 and week 64.
Time Frame week 32, week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Here, 'n' specifies the number of subjects with available data at specified timepoint.
Arm/Group Title Insulin Degludec/Insulin Glargine (IDeg/IGlar) Insulin Glargine/Insulin Degludec (IGlar/IDeg)
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 360 360
Mean (Standard Deviation)
Unit of Measure: mg/dL
week 32 (n=307, 311) 107.33  (41.72) 106.96  (39.81)
week 64 (n=293, 302) 114.07  (51.91) 107.55  (51.30)
Time Frame From the first day of exposure to randomised treatment and no later than the last day of randomised treatment (64 weeks)
Adverse Event Reporting Description 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.
 
Arm/Group Title Insulin Degludec (IDeg) Insulin Glargine (IGlar)
Hide Arm/Group Description 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). 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).
All-Cause Mortality
Insulin Degludec (IDeg) Insulin Glargine (IGlar)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Insulin Degludec (IDeg) Insulin Glargine (IGlar)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   64/671 (9.54%)      65/665 (9.77%)    
Blood and lymphatic system disorders     
Leukocytosis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Cardiac disorders     
Acute coronary syndrome  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Acute myocardial infarction  1  2/671 (0.30%)  2 1/665 (0.15%)  1
Angina pectoris  1  1/671 (0.15%)  1 4/665 (0.60%)  4
Angina unstable  1  0/671 (0.00%)  0 2/665 (0.30%)  2
Atrial fibrillation  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Cardiac failure  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Cardiac failure congestive  1  1/671 (0.15%)  1 2/665 (0.30%)  2
Coronary artery disease  1  2/671 (0.30%)  2 3/665 (0.45%)  3
Coronary artery dissection  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Coronary artery occlusion  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Intracardiac thrombus  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Myocardial infarction  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Myocardial ischaemia  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Supraventricular tachycardia  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Ventricular tachycardia  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Eye disorders     
Iridocyclitis  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Gastrointestinal disorders     
Colitis ischaemic  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Diarrhoea  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Diverticular fistula  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Flatulence  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Impaired gastric emptying  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Inguinal hernia  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Intestinal obstruction  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Pancreatitis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Small intestinal obstruction  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Vomiting  1  0/671 (0.00%)  0 1/665 (0.15%)  1
General disorders     
Chest discomfort  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Chest pain  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Lead dislodgement  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Non-cardiac chest pain  1  3/671 (0.45%)  3 3/665 (0.45%)  3
Hepatobiliary disorders     
Cholelithiasis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Hepatic cyst  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Jaundice cholestatic  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Infections and infestations     
Appendicitis  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Bronchitis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Bronchopulmonary aspergillosis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Cellulitis  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Cellulitis staphylococcal  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Cystitis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Diverticulitis  1  2/671 (0.30%)  2 0/665 (0.00%)  0
Gastroenteritis  1  1/671 (0.15%)  1 1/665 (0.15%)  1
Influenza  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Mastoiditis  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Ophthalmic herpes zoster  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Osteomyelitis  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Otitis externa  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Pneumonia  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Postoperative wound infection  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Salmonella sepsis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Sepsis  1  1/671 (0.15%)  1 4/665 (0.60%)  4
Staphylococcal sepsis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Urinary tract infection  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Injury, poisoning and procedural complications     
Ankle fracture  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Confusion postoperative  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Drug dispensing error  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Fall  1  1/671 (0.15%)  1 1/665 (0.15%)  1
Hip fracture  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Lumbar vertebral fracture  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Medication error  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Post lumbar puncture syndrome  1  1/671 (0.15%)  2 0/665 (0.00%)  0
Road traffic accident  1  2/671 (0.30%)  2 1/665 (0.15%)  1
Sternal fracture  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Toxicity to various agents  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Wrist fracture  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Investigations     
Computerised tomogram thorax abnormal  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  2/671 (0.30%)  2 1/665 (0.15%)  1
Electrolyte imbalance  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Hypoglycaemia  1  2/671 (0.30%)  2 9/665 (1.35%)  9
Hyponatraemia  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Musculoskeletal and connective tissue disorders     
Arthritis  1  2/671 (0.30%)  2 0/665 (0.00%)  0
Back pain  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Cervical spinal stenosis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Fibromyalgia  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Intervertebral disc protrusion  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Osteoarthritis  1  2/671 (0.30%)  2 1/665 (0.15%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Brain neoplasm  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Breast cancer  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Breast cancer stage I  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Colon cancer metastatic  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Lung adenocarcinoma  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Metastases to bone  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Non-Hodgkin's lymphoma  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Pancreatic carcinoma  1  2/671 (0.30%)  2 0/665 (0.00%)  0
Pituitary tumour benign  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Prostate cancer  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Squamous cell carcinoma  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Nervous system disorders     
Aphasia  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Carpal tunnel syndrome  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Cerebrovascular accident  1  1/671 (0.15%)  1 1/665 (0.15%)  1
Cervical radiculopathy  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Hypoglycaemic unconsciousness  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Ischaemic stroke  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Lacunar stroke  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Syncope  1  2/671 (0.30%)  2 1/665 (0.15%)  1
Thalamic infarction  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Toxic encephalopathy  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Transient ischaemic attack  1  0/671 (0.00%)  0 2/665 (0.30%)  2
Vertebral artery thrombosis  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Psychiatric disorders     
Abnormal behaviour  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Anxiety  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Bipolar I disorder  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Confusional state  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Mental status changes  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Panic attack  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Renal and urinary disorders     
Calculus bladder  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Nephrolithiasis  1  1/671 (0.15%)  1 1/665 (0.15%)  1
Renal cyst  1  0/671 (0.00%)  0 2/665 (0.30%)  2
Renal failure  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Reproductive system and breast disorders     
Ovarian mass  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/671 (0.15%)  1 2/665 (0.30%)  2
Chronic obstructive pulmonary disease  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Dyspnoea  1  1/671 (0.15%)  2 0/665 (0.00%)  0
Pleural effusion  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Pulmonary oedema  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Surgical and medical procedures     
Carpal tunnel decompression  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Mitral valve repair  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Prostatic operation  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Surgery  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Vascular disorders     
Aortic aneurysm  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Aortic stenosis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Deep vein thrombosis  1  0/671 (0.00%)  0 1/665 (0.15%)  1
Peripheral vascular disorder  1  1/671 (0.15%)  1 0/665 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Insulin Degludec (IDeg) Insulin Glargine (IGlar)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   93/671 (13.86%)      77/665 (11.58%)    
Infections and infestations     
Nasopharyngitis  1  50/671 (7.45%)  59 41/665 (6.17%)  49
Upper respiratory tract infection  1  44/671 (6.56%)  53 37/665 (5.56%)  44
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
EMail: clinicaltrials@novonordisk.com
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT02030600    
Other Study ID Numbers: NN1250-3998
U1111-1143-7963 ( Other Identifier: WHO )
First Submitted: January 7, 2014
First Posted: January 8, 2014
Results First Submitted: December 2, 2016
Results First Posted: January 30, 2017
Last Update Posted: May 10, 2019