Diabetes Mellitus, Type 2
Conditions
Brief summary
Primary Objective: To demonstrate the noninferiority in the efficacy of Toujeo® to Tresiba® in glycated hemoglobin (HbA1c) change from Baseline to Week 24. Secondary Objectives: Change From Baseline in HbA1c to Week 12 To assess the effects of the insulin Toujeo® in comparison with insulin Tresiba® at week 12 and week 24 on: * Change in Fasting plasma glucose (FPG); * Change in Fasting self-monitored plasma glucose (SMPG) and 4-point SMPG and 8-point SMPG profile; * Percentage of participants reaching HbA1c targets \<7% or ≤6.5%; * Percentage of participants reaching HbA1c targets \<7% or ≤6.5% without severe and/or confirmed hypoglycemia * Frequency of occurrence and diurnal distribution of hypoglycemia by American Diabetes Association (ADA) category of hypoglycemia. To assess the safety in each treatment group. To assess the treatment effects in each treatment group on Patient Reported Outcomes (PRO). Percentage of participants requiring rescue therapy.
Detailed description
The maximum study duration per participant was approximately 27 weeks: an up to 2-week screening period, a 24-week randomized treatment period (including 12 weeks active titration), and a 7-day posttreatment safety follow-up period.
Interventions
DRUGInsulin glargine, 300U/mL
Self-administered by subcutaneous (SC) injection in the evening using a pre-filled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 80 to 100 mg/dL (4.4 to 5.6 mmol/L).
DRUGInsulin degludec, 100 U/mL
Self-administered by subcutaneous (SC) injection in the evening using a pre-filled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 80 to 100 mg/dL (4.4 to 5.6 mmol/L). Route of administration: subcutaneous
DRUGNon-insulin anti-diabetic treatment
Background therapy: Oral Anti diabetics Drugs (OADs), Glucagon-like peptide-1 (GLP-1) receptor agonist.
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Adult participants with type 2 diabetes mellitus (T2DM) inadequately controlled with OADs therapy with/without GLP-1 receptor agonist at stable dose for at least 3 months. * Signed written informed consent.
Exclusion criteria
* Age \<18 years. * HbA1c \<7.5% or \>10.5% (at screening visit). Body mass index (BMI) \<25 kg/m\^2 or \>40 kg/m\^2. * History of T2DM for less than 1 year before screening. * Less than 6 months before screening on OADs treatment and GLP-1 receptor agonist (if taken). * Current or previous insulin use except for a maximum of 8 consecutive days or totally 15 days (eg, acute illness, surgery) during the last year prior to screening. * Initiation of new glucose-lowering medications and/or weight loss drug in the last 3 months before screening visit. * Participant receiving only noninsulin antihyperglycemic drugs not approved for combination with insulin according to local labelling/local treatment guideline. * History of hypoglycemia unawareness or repeated episodes of severe hypoglycemia or metabolic acidosis, including hospitalization for diabetic ketoacidosis during the last 12 months prior to screening. * Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (eg, laser, surgical treatment, or injectable drugs) during the study period. * End stage renal disease. * Any acute or chronic condition that in the opinion of Investigator would affect the safety of participant, compliance, or study results. * Any contraindication to use of Toujeo® or Tresiba® as defined in the national product label, hypersensitivity to Toujeo® or Tresiba® active ingredients or one of the excipients. * Pregnant or breast-feeding women. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c to Week 24 | Baseline, Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c to Week 12 | Baseline, Week 12 | 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. |
| Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 | Baseline, Week 12 and Week 24 | 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. |
| Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24 | Baseline, Week 12 and Week 24 | 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. |
| Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Baseline, Week 12 and Week 24 | 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. |
| Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point | Baseline, Week 12 and Week 24 | 4-point SMPG profiles were measured at the following 4 points: prebreakfast, prelunch, predinner and bedtime. |
| Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24 | Baseline, Week 12 and Week 24 | 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. |
| Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24 | Baseline, Week 12 and Week 24 | 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. |
| Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24 | Baseline, Week 12 and Week 24 | Adjusted LS means were obtained from MMRM. |
| 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 | Week 12, and Week 24 | 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 by plasma glucose =\<3.9 mmol/L (=\<70 mg/dL). |
| Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period | Baseline to Week 24 | 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. |
| Percentage of Participants Requiring a Rescue Therapy During 24 Weeks Treatment Period | Baseline to Week 24 | 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%. |
| Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24 | Baseline, Week 12 and Week 24 | Only the insulin dose measurements performed before initiation of rescue therapy and during the on-treatment period were considered in the analysis. |
| Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period | Day 1-Week 12, Week 13-Week 24, and 24 Week Period | 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. |
| Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period | Day 1-Week 12, Week 13-Week 24, and 24 Week Period | 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). |
| Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period | Day 1-Week 12, Week 13-Week 24, and 24 Week Period | 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). |
| Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period | Day 1-Week 12, Week 13-Week 24, and 24 Week Period | 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). |
| Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24 | Week 12, and Week 24 | Only the post-baseline HbA1c measurements before rescue and during the 12 week and 24-week on-treatment period were considered in the analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Diabetes Treatment Satisfaction Questionnaire (DTSQ) Status at Week 12 and Week 24 | Baseline, Week 12 and Week 24 | 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. |
Countries
Bulgaria, Croatia, Czechia, Denmark, France, Greece, Hungary, Israel, Italy, Romania, Serbia, Slovakia, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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').
Participants by arm
| Arm | Count |
|---|---|
| Toujeo Toujeo® (Insulin glargine, 300 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment. | 466 |
| Tresiba Tresiba® (Insulin Degludec, 100 U/mL) SC injection once daily up to Week 24 on top of non-insulin antidiabetic treatment. | 463 |
| Total | 929 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Hypoglycemia | 0 | 1 |
| Overall Study | Other than specified above | 11 | 21 |
| Overall Study | Poor Compliance to Protocol | 4 | 3 |
| Overall Study | Randomized but not treated | 4 | 1 |
Baseline characteristics
| Characteristic | Toujeo | Tresiba | Total |
|---|---|---|---|
| Age, Continuous | 60.6 years STANDARD_DEVIATION 9.6 | 60.5 years STANDARD_DEVIATION 9.8 | 60.5 years STANDARD_DEVIATION 9.7 |
| Basal Insulin Daily Dose | 0.19 Units per kilogram (U/kg) STANDARD_DEVIATION 0.04 | 0.12 Units per kilogram (U/kg) STANDARD_DEVIATION 0.03 | 0.15 Units per kilogram (U/kg) STANDARD_DEVIATION 0.05 |
| Baseline HbA1c | 8.71 Percentage of HbA1c STANDARD_DEVIATION 0.83 | 8.57 Percentage of HbA1c STANDARD_DEVIATION 0.8 | 8.64 Percentage of HbA1c STANDARD_DEVIATION 0.82 |
| Body Mass Index (BMI) | 31.7 Kg/m^2 STANDARD_DEVIATION 4.3 | 31.3 Kg/m^2 STANDARD_DEVIATION 4.4 | 31.5 Kg/m^2 STANDARD_DEVIATION 4.4 |
| Duration of Type 2 Diabetes Mellitus | 10.5 years STANDARD_DEVIATION 6.1 | 10.7 years STANDARD_DEVIATION 6.5 | 10.6 years STANDARD_DEVIATION 6.3 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 219 Participants | 211 Participants | 430 Participants |
| Sex: Female, Male Male | 247 Participants | 252 Participants | 499 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 462 | 0 / 462 |
| other Total, other adverse events | 56 / 462 | 58 / 462 |
| serious Total, serious adverse events | 21 / 462 | 20 / 462 |
Outcome results
Primary
Change From Baseline in HbA1c to Week 24
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Toujeo | Change From Baseline in HbA1c to Week 24 | -1.64 percentage of HbA1c | Standard Error 0.037 |
| Tresiba | Change From Baseline in HbA1c to Week 24 | -1.59 percentage of HbA1c | Standard Error 0.037 |
Comparison: A hierarchical step-down testing procedure was used to control type 1 error. Analysis was performed using a MMRM approach with treatment groups, randomization strata, visit, and treatment-by-visit interaction as fixed categorical effects and baseline HbA1c value and baseline HbA1c value-by-visit interaction as continuous fixed covariates.p-value: <0.000195% CI: [-0.152, 0.051]Mixed Models Analysis
Comparison: Superiority of Toujeo over Tresiba was demonstrated if the upper bound of the two-sided 95% CI for the difference in the mean change in HbA1c from baseline to Week 24 between Toujeo over Tresiba on ITT population was \<0 (zero).p-value: 0.330295% CI: [-0.152, 0.051]Mixed Models Analysis
Secondary
Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24 | Week 12 | -2.50 mmol/L | Standard Error 0.093 |
| Tresiba | Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24 | Week 24 | -2.53 mmol/L | Standard Error 0.096 |
Secondary
Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point
4-point SMPG profiles were measured at the following 4 points: prebreakfast, prelunch, predinner and bedtime.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 4.1 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: Bedtime | -2.10 mmol/L | Standard Deviation 4 |
| Tresiba | Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: Pre-breakfast | -2.97 mmol/L | Standard Deviation 2.62 |
| Tresiba | Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: Pre-breakfast | -2.99 mmol/L | Standard Deviation 2.81 |
| Tresiba | Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: Pre-lunch | -2.44 mmol/L | Standard Deviation 3.65 |
| Tresiba | Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: Pre-dinner | -1.86 mmol/L | Standard Deviation 4.01 |
| Tresiba | Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: Pre-dinner | -1.92 mmol/L | Standard Deviation 3.76 |
| Tresiba | Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: Pre-lunch | -2.26 mmol/L | Standard Deviation 3.92 |
| Tresiba | Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: Bedtime | -2.11 mmol/L | Standard Deviation 3.96 |
Secondary
Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 3.9 |
| Toujeo | 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 |
| Toujeo | 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 4.2 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: Bedtime | -2.09 mmol/L | Standard Deviation 3.96 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: Pre-dinner | -1.93 mmol/L | Standard Deviation 3.74 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: 03:00 at night | -2.43 mmol/L | Standard Deviation 3.51 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: 03:00 at night | -2.28 mmol/L | Standard Deviation 3.49 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: 2 hours after lunch | -1.93 mmol/L | Standard Deviation 3.91 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: Pre-breakfast | -3.00 mmol/L | Standard Deviation 2.63 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: Pre-breakfast | -3.03 mmol/L | Standard Deviation 2.85 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: 2 hours after breakfast | -3.23 mmol/L | Standard Deviation 3.92 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: 2 hours after dinner | -2.07 mmol/L | Standard Deviation 4 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: Pre-lunch | -2.50 mmol/L | Standard Deviation 3.65 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: 2 hours after breakfast | -3.50 mmol/L | Standard Deviation 4 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: 2 hours after lunch | -1.99 mmol/L | Standard Deviation 3.94 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: Pre-dinner | -1.86 mmol/L | Standard Deviation 4.01 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: 2 hours after dinner | -1.76 mmol/L | Standard Deviation 3.87 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 24: Pre-lunch | -2.29 mmol/L | Standard Deviation 3.93 |
| Tresiba | Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point | Week 12: Bedtime | -2.08 mmol/L | Standard Deviation 3.95 |
Secondary
Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24
Only the insulin dose measurements performed before initiation of rescue therapy and during the on-treatment period were considered in the analysis.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Toujeo | 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 0.2 |
| Toujeo | 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 |
| Tresiba | Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24 | Week 12 | 0.255 Units per kilogram (U/kg) | Standard Deviation 0.195 |
| Tresiba | Change From Baseline in Basal Insulin Dose (U/kg Body Weight) to Week 12 and Week 24 | Week 24 | 0.309 Units per kilogram (U/kg) | Standard Deviation 0.241 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Toujeo | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 | Week 12 | -3.64 mmol/L | Standard Error 0.099 |
| Toujeo | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 | Week 24 | -3.52 mmol/L | Standard Error 0.109 |
| Tresiba | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 | Week 12 | -3.89 mmol/L | Standard Error 0.1 |
| Tresiba | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 | Week 24 | -3.95 mmol/L | Standard Error 0.11 |
Secondary
Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24 | Week 12 | -3.25 mmol/L | Standard Error 0.067 |
| Tresiba | Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24 | Week 24 | -3.29 mmol/L | Standard Error 0.068 |
Secondary
Change From Baseline in HbA1c to Week 12
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Toujeo | Change From Baseline in HbA1c to Week 12 | -1.37 percentage of HbA1c | Standard Error 0.036 |
| Tresiba | Change From Baseline in HbA1c to Week 12 | -1.39 percentage of HbA1c | Standard Error 0.036 |
Secondary
Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24
Adjusted LS means were obtained from MMRM.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24 | Week 24 | 3.95 percentage of mean variability | Standard Error 0.599 |
| Tresiba | Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24 | Week 12 | 4.73 percentage of mean variability | Standard Error 0.561 |
Secondary
Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24 | Week 12 | 2.62 percentage of mean variability | Standard Error 0.416 |
| Tresiba | Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24 | Week 24 | 1.97 percentage of mean variability | Standard Error 0.39 |
Secondary
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period
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).
Time frame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | 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 | 0.91 Events per participant year |
| Tresiba | 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 | 0.88 Events per participant year |
| Tresiba | Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period | Any hypo Day1-Week12 | 11.31 Events per participant year |
| Tresiba | Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) Event Rate Per Participant Year During Study Period | Any hypo Week13-14 | 11.60 Events per participant year |
| Tresiba | 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 | 11.45 Events per participant year |
| Tresiba | 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 | 10.47 Events per participant year |
| Tresiba | 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 | 11.21 Events per participant year |
| Tresiba | 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 | 10.83 Events per participant year |
| Tresiba | 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 | 0.86 Events per participant year |
Secondary
Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period
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).
Time frame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | 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 | 0.22 Events per participant year |
| Tresiba | Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period | Any hypo D1-W12 | 2.36 Events per participant year |
| Tresiba | Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period | Any hypo W13-14 | 2.39 Events per participant year |
| Tresiba | Hypoglycemia (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal ) Event Rate Per Participant Year During Study Period | Any hypo 24Week period | 2.38 Events per participant year |
| Tresiba | 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 | 2.20 Events per participant year |
| Tresiba | 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 | 2.33 Events per participant year |
| Tresiba | 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 | 2.26 Events per participant year |
| Tresiba | 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 | 0.19 Events per participant year |
| Tresiba | 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 | 0.26 Events per participant year |
Secondary
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
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 by plasma glucose =\<3.9 mmol/L (=\<70 mg/dL).
Time frame: Week 12, and Week 24
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | 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% | 5.19 percentage of participants |
| Tresiba | 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% | 13.64 percentage of participants |
| Tresiba | 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% | 12.99 percentage of participants |
| Tresiba | 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% | 4.55 percentage of participants |
Secondary
Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24
Only the post-baseline HbA1c measurements before rescue and during the 12 week and 24-week on-treatment period were considered in the analysis.
Time frame: Week 12, and Week 24
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | 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 | 19.70 percentage of participants |
| Tresiba | 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 | 36.15 percentage of participants |
| Tresiba | 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 | 44.59 percentage of participants |
| Tresiba | 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 | 14.29 percentage of participants |
Secondary
Percentage of Participants Requiring a Rescue Therapy During 24 Weeks Treatment Period
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%.
Time frame: Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Toujeo | Percentage of Participants Requiring a Rescue Therapy During 24 Weeks Treatment Period | 1.30 percentage of participants |
| Tresiba | Percentage of Participants Requiring a Rescue Therapy During 24 Weeks Treatment Period | 1.30 percentage of participants |
Secondary
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Any Time of the Day) by Study Period
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.
Time frame: Day 1-Week 12, Week 13-Week 24, and 24 Week Period
Population: Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | 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 | 18.4 percentage of participants |
| Tresiba | 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 | 58.4 percentage of participants |
| Tresiba | 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 | 57.4 percentage of participants |
| Tresiba | 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 | 71.2 percentage of participants |
| Tresiba | 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 | 54.3 percentage of participants |
| Tresiba | 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 | 55.8 percentage of participants |
| Tresiba | 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 | 69.0 percentage of participants |
| Tresiba | 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 | 11.7 percentage of participants |
| Tresiba | 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 | 11.2 percentage of participants |
Secondary
Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | 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 |
| Tresiba | 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 | 18.8 percentage of participants |
| Tresiba | Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period | Any hypo 24Week period | 30.3 percentage of participants |
| Tresiba | 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 | 21.0 percentage of participants |
| Tresiba | 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 | 28.8 percentage of participants |
| Tresiba | 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 | 3.8 percentage of participants |
| Tresiba | Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period | Any hypo D1-W12 | 21.0 percentage of participants |
| Tresiba | 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 | 3.5 percentage of participants |
| Tresiba | Percentage of Participants With At Least One Hypoglycemic Events (Any, Severe and/or Confirmed Hypoglycemia: Nocturnal) by Study Period | Any hypo W13-14 | 21.2 percentage of participants |
Secondary
Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period
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.
Time frame: Baseline to Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Toujeo | Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period | 4.98 percentage of participants |
| Tresiba | Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period | 4.76 percentage of participants |
Other Pre-specified
Change From Baseline in Total Diabetes Treatment Satisfaction Questionnaire (DTSQ) Status at Week 12 and Week 24
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Toujeo | 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 |
| Toujeo | 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 |
| Tresiba | Change From Baseline in Total Diabetes Treatment Satisfaction Questionnaire (DTSQ) Status at Week 12 and Week 24 | Week 12 | 5.32 score on a scale | Standard Error 0.245 |
| Tresiba | Change From Baseline in Total Diabetes Treatment Satisfaction Questionnaire (DTSQ) Status at Week 12 and Week 24 | Week 24 | 5.44 score on a scale | Standard Error 0.256 |