Trial Outcomes & Findings for Comparison of Glucose Values and Variability Between TOUJEO and TRESIBA During Continuous Glucose Monitoring in Type 1 Diabetes Patients (NCT NCT04075513)

NCT ID: NCT04075513

Last Updated: 2022-11-14

Results Overview

The Continuous Glucose Monitoring (CGM) system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted least square (LS) means and standard error (SE) were obtained using analysis of covariance (ANCOVA) model on data obtained from the multiple imputations during Week 10 to Week 12.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 343 participants
• Primary outcome timeframe: During Week 10 up to Week 12
• Results posted on: 2022-11-14

Participant Flow

The study was conducted at 40 active sites in 7 countries. A total of 550 participants were screened between 09 October 2019 and 06 May 2021, of which 343 participants were enrolled and randomized by an interactive response technology (IRT) (1:1 ratio) to receive Toujeo or Tresiba. A total of 207 participants were screen failure mainly due to not meeting eligibility criteria.

Randomization was stratified by hemoglobin A1c (HbA1c) at screening (less than [<] 8.0 percent [%]; greater than or equal to [>=] 8.0%). Participants continued their short-acting mealtime insulin analogue (i.e., rapid insulin analogs) which they had used for at least 30 days before the screening visit and continued the same throughout the study.

Participant milestones

Measure	Toujeo Toujeo (Insulin Glargine, 300 units per milliliter \[U/ml\]) subcutaneous (SC) injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Overall Study STARTED	172	171
Overall Study COMPLETED	164	167
Overall Study NOT COMPLETED	8	4

Reasons for withdrawal

Measure	Toujeo Toujeo (Insulin Glargine, 300 units per milliliter \[U/ml\]) subcutaneous (SC) injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Overall Study Withdrawal by Subject	2	2
Overall Study Lack of Efficacy	1	0
Overall Study Lost to Follow-up	4	2
Overall Study Switch to insulin pump	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Toujeo n=172 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=171 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Total n=343 Participants Total of all reporting groups
Age, Continuous	42.9 years STANDARD_DEVIATION 13.53 • n=172 Participants	42.8 years STANDARD_DEVIATION 13.05 • n=171 Participants	42.8 years STANDARD_DEVIATION 13.28 • n=343 Participants
Sex: Female, Male Female	86 Participants n=172 Participants	74 Participants n=171 Participants	160 Participants n=343 Participants
Sex: Female, Male Male	86 Participants n=172 Participants	97 Participants n=171 Participants	183 Participants n=343 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: During Week 10 up to Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The Continuous Glucose Monitoring (CGM) system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted least square (LS) means and standard error (SE) were obtained using analysis of covariance (ANCOVA) model on data obtained from the multiple imputations during Week 10 to Week 12.

Outcome measures

Measure	Toujeo n=158 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=151 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Percentage of Time of Glucose Concentration Within the Target Range of Greater Than or Equal to (>=) 70 to Less Than or Equal to (<=) 180 Milligrams Per Deciliter: Non-inferiority Analysis	52.74 percentage of time Standard Error 0.859	55.09 percentage of time Standard Error 0.893

SECONDARY outcome

Timeframe: During Week 10 up to Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

CV% was a measure of spread of variability relative to mean of population. For CGM glucose values, CV% was measure of glycemic variability across 20 days and calculated as ratio of standard deviation of glucose values to mean of glucose values. LS means and SE were obtained using ANCOVA model using fixed categorical effects of treatment groups (Toujeo, Tresiba), randomization stratum of screening HbA1c (<8.0% versus >=8.0%), and the continuous fixed covariate of Baseline value.

Outcome measures

Measure	Toujeo n=158 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=151 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Glucose Total Coefficient of Variation (CV%)	39.91 percentage of total CV Standard Error 0.360	41.22 percentage of total CV Standard Error 0.373

SECONDARY outcome

Timeframe: During Week 10 up to Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted LS means and SE were obtained using ANCOVA model on data obtained from the multiple imputations during Week 10 to Week 12.

Outcome measures

Measure	Toujeo n=158 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=151 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Percentage of Time of Glucose Concentration Within the Target Range of >=70 to <=180 Milligrams Per Deciliter: Superiority Analysis	52.74 percentage of time Standard Error 0.859	55.09 percentage of time Standard Error 0.893

SECONDARY outcome

Timeframe: During Week 10 up to Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

CV% was a measure of spread of variability relative to mean of population. For CGM glucose values, CV% was measure of glycemic variability across 20 days and calculated within day and between days as ratio of standard deviation of glucose values to mean of glucose values. LS mean and SE were obtained from ANCOVA model including fixed categorical effects of treatment groups (TOUJEO, TRESIBA), randomization stratum of screening HbA1c (<8.0% versus >=8.0%), and as well as, the continuous fixed covariate of Baseline value.

Outcome measures

Measure	Toujeo n=158 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=151 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Glucose Within-day CV% and Between-day CV% Within-day CV%	33.48 percentage of CV Standard Error 0.342	34.37 percentage of CV Standard Error 0.351
Glucose Within-day CV% and Between-day CV% Between-day CV%	17.23 percentage of CV Standard Error 0.404	18.08 percentage of CV Standard Error 0.415

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Change in HbA1c at Week 12 was analyzed using an ANCOVA model including the fixed categorical effects of treatment groups (Toujeo, Tresiba), and the continuous fixed covariate of Baseline HbA1c value.

Outcome measures

Measure	Toujeo n=154 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=153 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 12	-0.75 percentage of HbA1c Standard Error 0.058	-0.92 percentage of HbA1c Standard Error 0.057

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Change in FPG was analyzed using an ANCOVA model including the fixed categorical effects of treatment groups (Toujeo, Tresiba) and the randomization stratum of HbA1c at screening (<8.0%, >=8.0%) and the continuous fixed covariate of Baseline FPG value.

Outcome measures

Measure	Toujeo n=154 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=151 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12	-16.05 milligrams per deciliter Standard Error 5.455	-34.55 milligrams per deciliter Standard Error 5.523

SECONDARY outcome

Timeframe: During Week 10 up to Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. "All time" represent the time between 00.00 hour to 23.59 hours and "night" represent the time between 00.00 hour to 05.59 hours. LS means and SE were obtained using ANCOVA model using fixed categorical effects of treatment groups (Toujeo, Tresiba), randomization stratum of screening HbA1c (<8.0% versus >=8.0%), and the continuous fixed covariate of Baseline value.

Outcome measures

Measure	Toujeo n=158 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=151 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Percentage of Time With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night) All time	5.55 percentage of time Standard Error 0.353	6.49 percentage of time Standard Error 0.362
Percentage of Time With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night) Night	6.32 percentage of time Standard Error 0.511	6.26 percentage of time Standard Error 0.524

SECONDARY outcome

Timeframe: During Week 10 up to Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

"All time" represent the time between 00.00 hour to 23.59 hours and "night" represent the time between 00.00 hour to 05.59 hours. Mean hours per day with glucose level <70 milligrams per deciliter during "all time" and only "during night" for the duration of Week 10 to Week 12 is reported in this outcome measure.

Outcome measures

Measure	Toujeo n=158 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=151 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Mean Hours Per Day With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night) All time	1.33 hours per day Standard Error 0.085	1.56 hours per day Standard Error 0.087
Mean Hours Per Day With Glucose Level <70 Milligrams Per Deciliter (All Time and During the Night) Night	0.38 hours per day Standard Error 0.031	0.38 hours per day Standard Error 0.031

SECONDARY outcome

Timeframe: During Week 10 up to Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. LS means and SE were obtained using ANCOVA model using fixed categorical effects of treatment groups (Toujeo, Tresiba), randomization stratum of screening HbA1c (<8.0% versus >=8.0%), and the continuous fixed covariate of Baseline value.

Outcome measures

Measure	Toujeo n=158 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=151 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Percentage of Time With Glucose Level >180 Milligrams Per Deciliter	41.52 percentage of time Standard Error 0.975	38.31 percentage of time Standard Error 1.002

SECONDARY outcome

Timeframe: During Week 10 up to Week 12

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Mean hours per day with glucose level >180 milligrams per deciliter for the duration of Week 10 to Week 12 is reported in this outcome measure.

Outcome measures

Measure	Toujeo n=158 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=151 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Mean Hours Per Day With Glucose Level >180 Milligrams Per Deciliter	9.96 hours per day Standard Error 0.234	9.19 hours per day Standard Error 0.240

SECONDARY outcome

Timeframe: From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days)

Population: Analysis was performed on safety population that included all randomized participants who had received at least one dose or part of a dose of IMP and were analyzed according to the treatment actually received.

Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <3.9 millimoles per liter (mmol/L) (<70 milligrams per deciliter). On-treatment period was defined as the time from the first injection of IMP (included) up to 2 days after the last injection of IMP.

Outcome measures

Measure	Toujeo n=172 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=171 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Number of Participants With at Least One Hypoglycemic Event During the On-treatment Period Any hypoglycemia	165 Participants	166 Participants
Number of Participants With at Least One Hypoglycemic Event During the On-treatment Period Severe hypoglycemia	8 Participants	10 Participants
Number of Participants With at Least One Hypoglycemic Event During the On-treatment Period Documented symptomatic hypoglycemia	136 Participants	134 Participants

SECONDARY outcome

Timeframe: From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days)

Population: Analysis was performed on safety population.

Number of hypoglycemia events (any, severe and documented) per participant-year of exposure were reported. Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <3.9 mmol/L (<70 milligrams per deciliter). On-treatment period was defined as the time from the first injection of IMP (included) up to 2 days after the last injection of IMP. Total participant years = The sum of the duration of exposure for all participants, expressed in participant years.

Outcome measures

Measure	Toujeo n=172 Participants Toujeo (Insulin Glargine, 300 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.	Tresiba n=171 Participants Tresiba (Insulin Degludec, 100 U/ml) SC injection, once daily in the morning before breakfast for 12 weeks on top of rapid acting insulin analog.
Number of Hypoglycemic Events Per Participant Year During the On-treatment Period Any hypoglycemia	109.4 events per participant-year	114.9 events per participant-year
Number of Hypoglycemic Events Per Participant Year During the On-treatment Period Severe hypoglycemia	0.2 events per participant-year	0.3 events per participant-year
Number of Hypoglycemic Events Per Participant Year During the On-treatment Period Documented symptomatic hypoglycemia	67.1 events per participant-year	66.9 events per participant-year

Adverse Events

Toujeo

Serious events: 7 serious events

Other events: 0 other events

Deaths: 0 deaths

Tresiba

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Toujeo n=172 participants at risk Toujeo (Insulin Glargine, 300 U/ml) SC injection, before meals once daily in the morning for 12 weeks on top of rapid acting insulin analog.	Tresiba n=171 participants at risk Tresiba (Insulin Degludec, 100 U/ml) SC injection, before meals once daily in the morning for 12 weeks on top of rapid acting insulin analog.
Metabolism and nutrition disorders Diabetic Ketoacidosis	0.00% 0/172 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.	0.58% 1/171 • Number of events 1 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/172 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.	2.3% 4/171 • Number of events 4 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.
Nervous system disorders Hypoglycaemic Seizure	1.2% 2/172 • Number of events 2 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.	0.00% 0/171 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.
Nervous system disorders Hypoglycaemic Unconsciousness	2.3% 4/172 • Number of events 4 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.	1.2% 2/171 • Number of events 3 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.
Nervous system disorders Orthostatic Intolerance	0.58% 1/172 • Number of events 1 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.	0.00% 0/171 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.00% 0/172 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.	0.58% 1/171 • Number of events 1 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/172 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.	0.58% 1/171 • Number of events 1 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.
Injury, poisoning and procedural complications Accidental Overdose	0.00% 0/172 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.	0.58% 1/171 • Number of events 1 • From the first injection of IMP up to 2 days after the last injection of IMP (i.e., up to 86 days) Reported AEs were TEAEs that developed/worsened or became serious during on-treatment period (defined as the time from the first injection of IMP to the last injection of IMP + 2 days). Analysis was performed on safety population.

Other adverse events

Adverse event data not reported

Additional Information

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