Trial Outcomes & Findings for Efficacy and Safety of Toujeo® Versus Tresiba® in Insulin-Naive Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Antihyperglycemic Drug(s) ± GLP-1 Receptor Agonist (NCT NCT02738151)

Last Updated: 2018-09-14

Results Overview

Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Adjusted Least Square (LS) means and standard errors were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data, using all post-baseline HbA1c data available during the 24-week on-treatment period.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

929 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2018-09-14

Participant Flow

The study was conducted at 158 study centers across 16 countries. A total of 1376 participants were screened between 19 May 2016 and 19 February 2017, of whom 447 were screen failures.

A total of 929 participants were randomized in 1:1 ratio to either Toujeo or Tresiba, stratified by screening glycated hemoglobin (HbA1c) values (\<8% or \>=8%); and use of sulfonylurea (SU) or meglitinides before the day of screening ('yes' versus 'no').

Participant milestones

Participant milestones
Measure	Toujeo Toujeo® (Insulin glargine, 300 U/mL) subcutaneous (SC) injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Overall Study STARTED	466	463
Overall Study Treated	462	462
Overall Study COMPLETED	443	432
Overall Study NOT COMPLETED	23	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Toujeo Toujeo® (Insulin glargine, 300 U/mL) subcutaneous (SC) injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Overall Study Randomized but not treated	4	1
Overall Study Adverse Event	4	5
Overall Study Hypoglycemia	0	1
Overall Study Poor Compliance to Protocol	4	3
Overall Study Other than specified above	11	21

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Toujeo n=466 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=463 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Total n=929 Participants Total of all reporting groups
Age, Continuous	60.6 years STANDARD_DEVIATION 9.6 • n=466 Participants	60.5 years STANDARD_DEVIATION 9.8 • n=463 Participants	60.5 years STANDARD_DEVIATION 9.7 • n=929 Participants
Sex: Female, Male Female	219 Participants n=466 Participants	211 Participants n=463 Participants	430 Participants n=929 Participants
Sex: Female, Male Male	247 Participants n=466 Participants	252 Participants n=463 Participants	499 Participants n=929 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Body Mass Index (BMI)	31.7 Kg/m^2 STANDARD_DEVIATION 4.3 • n=466 Participants	31.3 Kg/m^2 STANDARD_DEVIATION 4.4 • n=463 Participants	31.5 Kg/m^2 STANDARD_DEVIATION 4.4 • n=929 Participants
Duration of Type 2 Diabetes Mellitus	10.5 years STANDARD_DEVIATION 6.1 • n=466 Participants	10.7 years STANDARD_DEVIATION 6.5 • n=463 Participants	10.6 years STANDARD_DEVIATION 6.3 • n=929 Participants
Baseline HbA1c	8.71 Percentage of HbA1c STANDARD_DEVIATION 0.83 • n=466 Participants	8.57 Percentage of HbA1c STANDARD_DEVIATION 0.80 • n=463 Participants	8.64 Percentage of HbA1c STANDARD_DEVIATION 0.82 • n=929 Participants
Basal Insulin Daily Dose	0.19 Units per kilogram (U/kg) STANDARD_DEVIATION 0.04 • n=461 Participants • Number of participants analyzed = participants with available data for specified measure.	0.12 Units per kilogram (U/kg) STANDARD_DEVIATION 0.03 • n=461 Participants • Number of participants analyzed = participants with available data for specified measure.	0.15 Units per kilogram (U/kg) STANDARD_DEVIATION 0.05 • n=922 Participants • Number of participants analyzed = participants with available data for specified measure.

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-treat(ITT) population: all randomized participants who received at least 1 dose of IMP, regardless of whether treatment was actually being received \& analyzed as per allocated treatment group. Overall number of participants analyzed=participants with at least 1 baseline \& 1 post-baseline HbA1c assessment during 24week on-treatment period.

Outcome measures

Outcome measures
Measure	Toujeo n=430 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=425 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in HbA1c to Week 24	-1.64 percentage of HbA1c Standard Error 0.037	-1.59 percentage of HbA1c Standard Error 0.037

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Here, overall number of participants analyzed = participants with at least one baseline and one post-baseline HbA1c assessment during the 12 week on-treatment period.

Change in HbA1c was calculated by subtracting baseline value from Week 12 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with MMRM.

Outcome measures

Outcome measures
Measure	Toujeo n=448 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=445 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in HbA1c to Week 12	-1.37 percentage of HbA1c Standard Error 0.036	-1.39 percentage of HbA1c Standard Error 0.036

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Here, number analyzed = participants with at least one baseline and one post baseline FPG values at specified timepoints.

Change in FPG was calculated by subtracting baseline value from Week 12 and Week 24 value. Adjusted LS means were obtained from MMRM including post baseline values during the 24-week on-treatment period.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 Week 12	-3.64 mmol/L Standard Error 0.099	-3.89 mmol/L Standard Error 0.100
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 Week 24	-3.52 mmol/L Standard Error 0.109	-3.95 mmol/L Standard Error 0.110

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Here, overall number analyzed =participants with at least one baseline and one post baseline fasting SMPG values at specified timepoints.

Fasting SMPG was measured by the participant before breakfast and before the administration of the glucose-lowering agents once a day during the study. Adjusted LS means were obtained from MMRM including post baseline values during the 24 week on treatment period.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24 Week 12	-3.26 mmol/L Standard Error 0.067	-3.25 mmol/L Standard Error 0.067
Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24 Week 24	-3.23 mmol/L Standard Error 0.067	-3.29 mmol/L Standard Error 0.068

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Number Analyzed = participants with at least one baseline and one post baseline 8 Point SMPG values at specified time point.

8-point SMPG profiles were measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: 03:00 at night	-2.77 mmol/L Standard Deviation 3.16	-2.28 mmol/L Standard Deviation 3.49
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: Pre-breakfast	-3.42 mmol/L Standard Deviation 2.79	-3.00 mmol/L Standard Deviation 2.63
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: 2 hours after breakfast	-3.20 mmol/L Standard Deviation 4.02	-3.23 mmol/L Standard Deviation 3.92
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: Pre-lunch	-2.64 mmol/L Standard Deviation 3.90	-2.50 mmol/L Standard Deviation 3.65
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: 2 hours after lunch	-2.51 mmol/L Standard Deviation 4.15	-1.99 mmol/L Standard Deviation 3.94
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: Pre-dinner	-2.04 mmol/L Standard Deviation 3.63	-1.93 mmol/L Standard Deviation 3.74
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: 2 hours after dinner	-2.32 mmol/L Standard Deviation 4.20	-1.76 mmol/L Standard Deviation 3.87
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: Bedtime	-2.44 mmol/L Standard Deviation 4.07	-2.08 mmol/L Standard Deviation 3.95
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: 03:00 at night	-2.65 mmol/L Standard Deviation 3.43	-2.43 mmol/L Standard Deviation 3.51
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: Pre-breakfast	-3.37 mmol/L Standard Deviation 2.81	-3.03 mmol/L Standard Deviation 2.85
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: 2 hours after breakfast	-3.30 mmol/L Standard Deviation 3.68	-3.50 mmol/L Standard Deviation 4.00
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: Pre-lunch	-2.81 mmol/L Standard Deviation 3.67	-2.29 mmol/L Standard Deviation 3.93
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: 2 hours after lunch	-2.74 mmol/L Standard Deviation 3.73	-1.93 mmol/L Standard Deviation 3.91
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: Pre-dinner	-1.87 mmol/L Standard Deviation 3.78	-1.86 mmol/L Standard Deviation 4.01
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: 2 hours after dinner	-2.28 mmol/L Standard Deviation 4.19	-2.07 mmol/L Standard Deviation 4.00
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: Bedtime	-2.52 mmol/L Standard Deviation 3.87	-2.09 mmol/L Standard Deviation 3.96

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Number analyzed = Participants with at least one baseline and one post-baseline 4-point SMPG values at specified timepoints.

4-point SMPG profiles were measured at the following 4 points: prebreakfast, prelunch, predinner and bedtime.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: Bedtime	-2.51 mmol/L Standard Deviation 3.87	-2.10 mmol/L Standard Deviation 4.00
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: Pre-breakfast	-3.41 mmol/L Standard Deviation 2.75	-2.97 mmol/L Standard Deviation 2.62
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: Pre-lunch	-2.63 mmol/L Standard Deviation 3.88	-2.44 mmol/L Standard Deviation 3.65
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: Pre-dinner	-2.03 mmol/L Standard Deviation 3.64	-1.92 mmol/L Standard Deviation 3.76
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Week 12: Bedtime	-2.41 mmol/L Standard Deviation 4.10	-2.11 mmol/L Standard Deviation 3.96
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: Pre-breakfast	-3.38 mmol/L Standard Deviation 2.81	-2.99 mmol/L Standard Deviation 2.81
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: Pre-lunch	-2.81 mmol/L Standard Deviation 3.67	-2.26 mmol/L Standard Deviation 3.92
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Week 24: Pre-dinner	-1.88 mmol/L Standard Deviation 3.79	-1.86 mmol/L Standard Deviation 4.01

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Here, number analyzed = Participants with at least one baseline and one post-baseline 24-hour average SMPG values at specified time points.

The 8-point SMPG profile was measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Adjusted LS means were obtained from MMRM.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24 Week 12	-2.57 mmol/L Standard Error 0.092	-2.50 mmol/L Standard Error 0.093
Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24 Week 24	-2.62 mmol/L Standard Error 0.094	-2.53 mmol/L Standard Error 0.096

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Number Analyzed = participants with at least one baseline and one post baseline Fasting SMPG values at specified time point.

Adjusted LS means were obtained from MMRM. Variability was assessed by the mean of coefficient of variation calculated over at least 3 SMPG measured during the 7 days preceding the given visit.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24 Week 12	2.38 percentage of mean variability Standard Error 0.418	2.62 percentage of mean variability Standard Error 0.416
Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24 Week 24	1.49 percentage of mean variability Standard Error 0.391	1.97 percentage of mean variability Standard Error 0.390

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Here, number analyzed = Participants with at least one baseline and one post-baseline 24-hour average SMPG values at specified time points.

Adjusted LS means were obtained from MMRM.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24 Week 12	4.08 percentage of mean variability Standard Error 0.562	4.73 percentage of mean variability Standard Error 0.561
Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24 Week 24	3.70 percentage of mean variability Standard Error 0.588	3.95 percentage of mean variability Standard Error 0.599

SECONDARY outcome

Timeframe: Week 12, and Week 24

Population: ITT population.

Only the post-baseline HbA1c measurements before rescue and during the 12 week and 24-week on-treatment period were considered in the analysis.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24 Participants who reached the target <7% at Week 12	34.63 percentage of participants	36.15 percentage of participants
Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24 Participants who reached target <=6.5% at Week 12	11.47 percentage of participants	14.29 percentage of participants
Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24 Participants who reached the target <7% at Week 24	48.70 percentage of participants	44.59 percentage of participants
Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24 Participants who reached target <=6.5% at Week 24	21.21 percentage of participants	19.70 percentage of participants

SECONDARY outcome

Timeframe: Week 12, and Week 24

Population: ITT population.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Percentage of Participants Reaching Target HbA1c <7% and =<6.5% at Week 12 and Week 24 Without Severe and/or Confirmed Hypoglycemia (70 mg/dL) Event Week12: Participants who reached the target <7%	16.45 percentage of participants	13.64 percentage of participants
Percentage of Participants Reaching Target HbA1c <7% and =<6.5% at Week 12 and Week 24 Without Severe and/or Confirmed Hypoglycemia (70 mg/dL) Event Week12: Participants who reached target <=6.5%	4.11 percentage of participants	4.55 percentage of participants
Percentage of Participants Reaching Target HbA1c <7% and =<6.5% at Week 12 and Week 24 Without Severe and/or Confirmed Hypoglycemia (70 mg/dL) Event Week24: Participants who reached the target <7%	13.42 percentage of participants	12.99 percentage of participants
Percentage of Participants Reaching Target HbA1c <7% and =<6.5% at Week 12 and Week 24 Without Severe and/or Confirmed Hypoglycemia (70 mg/dL) Event Week24: Participants who reached target <=6.5%	5.84 percentage of participants	5.19 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: ITT population.

Percentage of participants With Sulphonylurea or Meglitinide dose reduction/ discontinuation due to Hypoglycemia during 24 Week treatment period were reported. Only participants with Sulphonylurea or meglitinides at Screening as per actual strata were taken into account in this analysis.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period	4.98 percentage of participants	4.76 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: ITT population.

Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. Threshold values at Week 12: FPG \>200 mg/dL (11 mmol/L), or HbA1c \>8.5%.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Percentage of Participants Requiring a Rescue Therapy During 24 Weeks Treatment Period	1.30 percentage of participants	1.30 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: Safety population included all randomized participants who did actually receive at least one dose of IMP, regardless of the amount of treatment administered.

Only the insulin dose measurements performed before initiation of rescue therapy and during the on-treatment period were considered in the analysis.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24 Week 12	0.289 Units per kilogram (U/kg) Standard Deviation 0.200	0.255 Units per kilogram (U/kg) Standard Deviation 0.195
Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24 Week 24	0.357 Units per kilogram (U/kg) Standard Deviation 0.253	0.309 Units per kilogram (U/kg) Standard Deviation 0.241

SECONDARY outcome

Timeframe: Day 1-Week 12, Week 13-Week 24, and 24 Week Period

Population: Safety population.

Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =\<70 mg/dL (=\<3.9 mmol/L), or \< 54 mg/dL (\<3.0 mmol/L). Assessment was done by treatment period (for =\<12 weeks, for \>12 weeks to =\<24 weeks (24W)). Percentage of participants with at least one hypoglycemia (hypo) event at any time of the day were reported.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Severe and/or confirmed hypo (=<70mg/dL) W13-14	54.1 percentage of participants	55.8 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Severe and/or confirmed hypo( <54 mg/dL) W13-14	9.8 percentage of participants	11.2 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Severe and/or confirmed hypo (<54mg/dL) 24W period	14.7 percentage of participants	18.4 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Any hypo 24 week period	70.1 percentage of participants	71.2 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Severe and/or confirmed hypo (=<70mg/dL) D1-W12	47.4 percentage of participants	54.3 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Severe and/or confirmed hypo(=<70mg/dL) 24W period	66.5 percentage of participants	69.0 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Severe and/or confirmed hypo (< 54mg/dL) D1-W12	7.8 percentage of participants	11.7 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Any hypo Day1-Week 12	53.0 percentage of participants	58.4 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period Any hypo Week13-14	57.2 percentage of participants	57.4 percentage of participants

SECONDARY outcome

Timeframe: Day 1-Week 12, Week 13-Week 24, and 24 Week Period

Population: Safety population included all randomized participants who did actually receive at least one dose of IMP, regardless of the amount of treatment administered.

Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycaemia event was a severe event or an event confirmed with plasma glucose =\<70 mg/dL (=\<3.9 mmol/L), or \< 54 mg/dL (\<3.0 mmol/L). Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time). Assessment was done by treatment period (for =\<12 weeks, for \>12 weeks to =\<24 weeks).

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Any hypo D1-W12	18.4 percentage of participants	21.0 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Any hypo 24Week period	31.2 percentage of participants	30.3 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Severe and/or confirmed hypo (=<70mg/dL)D1-W12	15.2 percentage of participants	18.8 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Severe and/or confirmed hypo (=<70mg/dL)W13-14	21.4 percentage of participants	21.0 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Severe and/or confirmed hypo(< 54mg/dL)W13-14	4.5 percentage of participants	3.8 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Severe and/or confirmed hypo(< 54mg/dL)24W Period	6.1 percentage of participants	6.1 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Any hypo W13-14	22.7 percentage of participants	21.2 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Severe and/or confirmed hypo(=<70mg/dL)24W Period	28.6 percentage of participants	28.8 percentage of participants
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period Severe and/or confirmed hypo(< 54mg/dL)D1-W12	2.8 percentage of participants	3.5 percentage of participants

SECONDARY outcome

Timeframe: Day 1-Week 12, Week 13-Week 24, and 24 Week Period

Population: Safety population

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Any hypo Week13-14	11.28 Events per participant year	11.60 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Any hypo 24 Week period	10.09 Events per participant year	11.45 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo (=<70mg/dL) D1-W12	8.08 Events per participant year	10.47 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Any hypo Day1-Week12	8.93 Events per participant year	11.31 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo (=<70mg/dL) W13-14	10.64 Events per participant year	11.21 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo (≤70mg/dL) 24W period	9.34 Events per participant year	10.83 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo (< 54mg/dL) D1-W12	0.49 Events per participant year	0.86 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo( <54 mg/dL) W13-14	0.73 Events per participant year	0.91 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo (<54mg/dL) 24W period	0.61 Events per participant year	0.88 Events per participant year

SECONDARY outcome

Timeframe: Day 1-Week 12, Week 13-Week 24, and 24 Week Period

Population: Safety population

Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed with plasma glucose =\<70 mg/dL (=\<3.9 mmol/L), or \< 54 mg/dL (\<3.0 mmol/L). Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time).

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo(=<70mg/dL)D1-W12	1.42 Events per participant year	2.20 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo(=<70mg/dL)W13-14	2.24 Events per participant year	2.33 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo(=<70mg/dL)24W Period	1.83 Events per participant year	2.26 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo(< 54mg/dL)W13-14	0.33 Events per participant year	0.26 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo(< 54mg/dL)D1-W12	0.16 Events per participant year	0.19 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Any hypo D1-W12	1.65 Events per participant year	2.36 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Any hypo W13-14	2.32 Events per participant year	2.39 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Any hypo 24Week period	1.98 Events per participant year	2.38 Events per participant year
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period Severe and/or confirmed hypo(< 54mg/dL)24W Period	0.24 Events per participant year	0.22 Events per participant year

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Number Analyzed = participants with at least one baseline and one post-baseline DTSQ status (DTSQs) total score.

The DTSQs is a validated questionnaire to assess participant's satisfaction with their diabetes treatment. It consists of 8 items that are answered on a Likert scale from 0 to 6. Total treatment satisfaction score is the sum of items 1, 4-8 scores and ranged from 0 (no satisfaction) to 36 (high satisfaction with treatment). Adjusted least square means and standard errors were obtained from a mixed-effect model with MMRM.

Outcome measures

Outcome measures
Measure	Toujeo n=462 Participants Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 Participants Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Change From Baseline in Total Diabetes Treatment Satisfaction Questionnaire (DTSQ) Status at Week 12 and Week 24 Week 12	5.08 score on a scale Standard Error 0.246	5.32 score on a scale Standard Error 0.245
Change From Baseline in Total Diabetes Treatment Satisfaction Questionnaire (DTSQ) Status at Week 12 and Week 24 Week 24	5.77 score on a scale Standard Error 0.257	5.44 score on a scale Standard Error 0.256

Adverse Events

Toujeo

Serious events: 21 serious events

Other events: 56 other events

Deaths: 1 deaths

Tresiba

Serious events: 20 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Toujeo n=462 participants at risk Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.	Tresiba n=462 participants at risk Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment.
Infections and infestations Upper Respiratory Tract Infection	5.2% 24/462 • Number of events 25 • All Adverse Events were collected from signature of the informed consent form until 7 days after last treatment administration (maximum exposure: 24 Weeks). Reported adverse events and death were treatment-emergent adverse events that is adverse events that developed/worsened during the 'on treatment period' (On-treatment period was defined as the time from the first injection of open-label Investigational Medicinal Product (IMP) up to 7 days after the last injection of open-label IMP, regardless of the introduction of rescue therapy). Analysis was performed on safety population.	4.1% 19/462 • Number of events 20 • All Adverse Events were collected from signature of the informed consent form until 7 days after last treatment administration (maximum exposure: 24 Weeks). Reported adverse events and death were treatment-emergent adverse events that is adverse events that developed/worsened during the 'on treatment period' (On-treatment period was defined as the time from the first injection of open-label Investigational Medicinal Product (IMP) up to 7 days after the last injection of open-label IMP, regardless of the introduction of rescue therapy). Analysis was performed on safety population.
Infections and infestations Viral Upper Respiratory Tract Infection	8.2% 38/462 • Number of events 49 • All Adverse Events were collected from signature of the informed consent form until 7 days after last treatment administration (maximum exposure: 24 Weeks). Reported adverse events and death were treatment-emergent adverse events that is adverse events that developed/worsened during the 'on treatment period' (On-treatment period was defined as the time from the first injection of open-label Investigational Medicinal Product (IMP) up to 7 days after the last injection of open-label IMP, regardless of the introduction of rescue therapy). Analysis was performed on safety population.	8.7% 40/462 • Number of events 45 • All Adverse Events were collected from signature of the informed consent form until 7 days after last treatment administration (maximum exposure: 24 Weeks). Reported adverse events and death were treatment-emergent adverse events that is adverse events that developed/worsened during the 'on treatment period' (On-treatment period was defined as the time from the first injection of open-label Investigational Medicinal Product (IMP) up to 7 days after the last injection of open-label IMP, regardless of the introduction of rescue therapy). Analysis was performed on safety population.

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER