Type 2 Diabetes Mellitus
Conditions
Brief summary
This was a parallel-group treatment, Phase 3, randomized, 2-arm study that assessed the efficacy and safety of iGlarLixi to IDegAsp in Chinese T2DM participants insufficiently controlled with oral antidiabetic drug(s). Study details included: * Study duration per participant: approximately up to 27 weeks * Treatment duration: 24 weeks * Visit frequency: after screening (an on-site visit), on-site or phone call visit every 1 week from randomization till Week 4, every 2 weeks till week 12 and then every 3 weeks till Week 24 (End of Treatment). There were 14 visits that included 7 phone calls and 7 on-site visits in total during screening and treatment periods. There was a safety follow-up by a phone call visit (End of Study) in 3 days after the last dose of the treatment. * Health measurement/Observation: change in HbA1c as the primary endpoint. * Intervention name: iGlarLixi and IDegAsp * Participant sex: male and female * Participant age range: adults at least 18 years of age * Condition/disease: Type 2 diabetes mellitus
Detailed description
27 weeks
Interventions
solution, by subcutaneous injection
DRUGIDegAsp
solution, by subcutaneous injection
DRUGMetformin
Tablet, orally
DRUGSGLT2 inhibitor
Tablet, orally
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
* Participant had at least 18 of age inclusive, at the time of signing the informed consent. * Participants who were diagnosed with T2DM for at least 1 year before the screening visit * Participants who were treated for at least 3 months prior to the screening visit with a stable dose of metformin (at least 1000 mg/day or the maximum tolerated dose) alone or in combination with a second oral antidiabetic treatment that can be a sulfonylurea (SU), a glinide, an alpha-glucosidase inhibitor (alpha-GI), a dipeptidyl-peptidase-4 (DPP-4) inhibitor or a sodium-glucose co-transporter 2 (SGLT-2) inhibitor * HbA1c at screening visit: * between 7.5% and 11%, both inclusive, for participants previously treated with metformin alone or + SGLT-2 inhibitor, or * between 7.0% and 10%, both inclusive, for participants previously treated with metformin + a second oral antidiabetic treatment other than SGLT-2 inhibitor. * Participants who were overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. * Body mass index (BMI) \<40 kg/m² at screening * Male or female, including females of childbearing potential who agreed to use contraception during the study duration * Participants were capable of giving signed informed consent as described in Appendix 1 of the protocol which included compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria
* Participant who had a severe renal function impairment with an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m² * Pregnant or breast-feeding woman. * Woman of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to be tested for pregnancy * Conditions/situations such as: * Participant with short life expectancy. * Participant with conditions/concomitant diseases making him/her not evaluable for the primary efficacy endpoint (eg, hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to screening). * Participant with conditions/concomitant diseases precluding his/her safe participation in this study (eg, active malignant tumor, major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require laser treatment within the study period). * Uncooperative or any condition that could make the participant potentially non-compliant to the study procedures (e.g., participant unable or unwilling to do self-injections or blood glucose monitoring using the Sponsor-provided blood glucometer at home). * Previous treatment with insulin (except for short-term treatment ≤14 days due to intercurrent illness at the discretion of the Investigator) within 1 year prior to screening. * Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria within 3 months prior to screening. * Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to screening. * Use of weight loss drugs within 3 months prior to screening. * History of discontinuation of a previous treatment with GLP-1 RAs due to safety/tolerability reasons or lack of efficacy. * Use of any investigational drug other than specified in this protocol within 1 month or 5 half-lives, whichever is longer, prior to screening. * Laboratory findings tested at the screening visit: * Amylase and/or lipase \>3 times the upper limit of normal (ULN) laboratory range. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 ULN. * Total bilirubin \>1.5 ULN (except in case of Gilbert's syndrome). * Calcitonin ≥20 pg/mL (5.9 pmol/L). * Hemoglobin \<10.5 g/dL and/or neutrophils \<1500/mm\^3 and/or platelets \<100 000/mm\^3. * Positive urine pregnancy test in female of childbearing potential. * Contraindication to metformin and/or SGLT-2 inhibitor use, for those who were taking it prior to the study, according to local labeling, warning/precaution of use (when appropriate) as displayed in the respective National regulation * Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized * Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures * Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with section 1.61 of the ICH-GCP Ordinance E6) * Any specific situation during study implementation/course that may raise ethics considerations * Sensitivity to any of the study interventions (insulin or, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study * Participants who withdrawn consent at randomization or were lost to follow up at randomization visit. The above information was not intended to contain all considerations relevant to a potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to Week 24: Non-Inferiority Analysis | Baseline, Week 24 | Blood samples were collected at indicated timepoints for analysis of HbA1c. Baseline was defined as the last available pre-dose assessment (on or before Day 1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight From Baseline to Week 24 | Baseline, Week 24 | Body weight was obtained with the participant wearing undergarments or very light clothing and no shoes, and with an empty bladder. The same scale was used throughout the study. Baseline was defined as the last available pre-dose assessment (on or before Day 1). |
| Percentage of Participants Reaching HbA1c <7% at Week 24 | Week 24 | Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c value were considered as non-responders. Percentages are rounded off to the tenth decimal place. |
| Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 | Week 24 | Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c or body weight value were considered as non-responders. Percentages are rounded off to the tenth decimal place. |
| Hypoglycemic Event Rate During the On-Treatment Period | From first dose of study drug up to 1 day after the last administration of study drug (maximum treatment exposure: 192 days) | During the study, participants were instructed to document the presence of hypoglycemic episodes in their study diary. Percentage of hypoglycemic events per participant-year during on-treatment period are reported. The on-treatment period (TE period) was defined as the period from the first injection study treatment to the last injection of study treatment + 3 days (1 day for hypoglycemia). |
| Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 and no Hypoglycemia During 24-Week Treatment Period | Baseline up to Week 24 | Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c or body weight value were considered as non-responders. During the study, participants were instructed to document the presence of hypoglycemic episodes in their study diary. Hypoglycemia was characterized as per American Diabetes Association (ADA) 2021 recommendations. * ADA Level 1 hypoglycemia: A measurable glucose concentration \<70 milligram/deciliter (mg/dL) (3.9 millimoles/liter \[mmol/L\]) but \>=54 mg/dL (3.0 mmol/L). * ADA Level 2 hypoglycemia: Blood glucose concentration \<54 mg/dL \[3.0 mmol/L\]; the threshold at which neuroglycopenic symptoms begin to occur and requires immediate action to resolve the hypoglycemic event. * ADA Level 3 hypoglycemia: A severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. Percentages are rounded off to the tenth decimal place. |
| Change in Fasting Plasma Glucose From Baseline to Week 24 | Baseline, Week 24 | Blood samples were collected at fasting state (no food or drinks \[except water\] for at least 8 hours) at indicated timepoints. Baseline was defined as the last available pre-dose assessment (on or before Day 1). |
| Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 24 | Baseline, Week 24 | Participants were provided with a glucometer, corresponding supplies, a leaflet, and with diaries in order to perform self-measurement of plasma glucose and its recording and were trained on how to use the glucometer. The 7-point SMPG profile was measured at the following 7-points: pre-prandial (before starting a meal) and 2 hours postprandial each for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal. The participants performed 7-point SMPG profile measurement over a single 24-hour period on 2 different days in the week. Baseline was defined as the last available pre-dose assessment (on or before Day 1). |
| Percentage of Participants Reaching HbA1c <7% at Week 24 With no Hypoglycemia During 24-Week Treatment Period | Baseline up to Week 24 | Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c value were considered as non-responders. Hypoglycemia was characterized as per ADA 2021 recommendations. * ADA Level 1 hypoglycemia: A measurable glucose concentration \<70 mg/dL (3.9 mmol/L) but \>=54 mg/dL (3.0 mmol/L). * ADA Level 2 hypoglycemia: Blood glucose concentration \<54mg/dL \[3.0 mmol/L\]; the threshold at which neuroglycopenic symptoms begin to occur and requires immediate action to resolve the hypoglycemic event. * ADA Level 3 hypoglycemia: A severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. Percentages are rounded off to the tenth decimal place. |
| Change in HbA1c From Baseline to Week 24: Superiority Analysis | Baseline, Week 24 | Blood samples were collected at indicated timepoints for analysis of HbA1c. Baseline was defined as the last available pre-dose assessment (on or before Day 1). |
| Total Daily Insulin Dose at Week 24 | Week 24 | Total daily insulin dose was defined as the sum of the insulin dose from study treatment and non-study treatment (e.g., rescue therapy). It was the average of the last 3 available insulin doses recorded in the electronic case report form in the week before visit. |
| Percentage of Participants Who Required Rescue Therapy During the 24-Week Treatment Period | Baseline up to Week 24 | Routine HbA1c value was used to determine the requirement of rescue medication. Threshold value was HbA1c \>8% at Week 12 or later on despite appropriate corrective actions. Percentages are rounded off to the tenth decimal place. |
| Change in Fasting C-Peptide From Baseline to Week 24 | Baseline, Week 24 | Blood samples were collected at fasting state (no food or drinks \[except water\] for at least 8 hours) at indicated timepoints. Baseline was defined as the last available pre-dose assessment (on or before Day 1). |
| Number of Participants With Any Hypoglycemia Event During On-Treatment Period | From first dose of study drug up to 1 day after the last administration of study drug (maximum treatment exposure: 192 days) | During the study, participants were instructed to document the presence of hypoglycemic episodes in their study diary. Number of participants who met ADA definition of hypoglycemia during the treatment period are reported. * ADA Level 1 hypoglycemia: A measurable glucose concentration \<70 mg/dL (3.9 mmol/L) but \>=54 mg/dL (3.0 mmol/L). * ADA Level 2 hypoglycemia: Blood glucose concentration \<54mg/dL \[3.0 mmol/L\]; the threshold at which neuroglycopenic symptoms begin to occur and requires immediate action to resolve the hypoglycemic event. * ADA Level 3 hypoglycemia: A severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. The on-treatment period (ie, treatment-emergent \[TE\] period) was defined as the period from the first injection study treatment to the last injection of study treatment + 3 days (1 day for hypoglycemia). |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation | From signature of the informed consent form up to the final visit regardless of seriousness or relationship to study drug (maximum treatment exposure: 192 days) | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any adverse event that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was a suspected transmission of any infectious agent via an authorized medicinal product. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. TE period was defined as the period from the first injection study treatment to the last injection of study treatment + 3 days. |
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | From first dose of study drug up to 3 days after last administration of study drug (maximum treatment exposure: 192 days) | Vital signs assessments included systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) in sitting position with their arm outstretched in line with mid-sternum and supported and weight. Criteria for PCSA: SBP: \<=95 millimeters of mercury (mmHg) and decrease from baseline \>=20 mmHg, \>=160 mmHg and increase from baseline \>=20 mmHg; DBP :\<=45 mmHg and decrease from baseline \>=10 mmHg,\>=110 mmHg and increase from baseline \>=10 mmHg; HR: \<=50 beats/min and decrease from baseline \>=20 beats/min,\>=120 beats/min and increase from baseline \>=20 beats/min; Weight \>=5% decrease from baseline, \>=5% increase from baseline. |
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | From first dose of study drug up to 3 days after last administration of study drug (maximum treatment exposure: 192 days) | Criteria for PCSA: For Hemoglobin (Hb), there are 3 criteria: (1)\<=115 grams (g)/L (Male\[M\]) or \<=95 g/L (Female\[F\]), (2)\>= 185 g/L (M) or \>=165 g/L (F), and (3) decrease from baseline \>=20 g/L; Hematocrit: \<=0.37 volume/volume (v/v) (M) or \<=0.32 v/v (F), \>=0.55 v/v (M) or \>=0.5 v/v (F); Red blood cells (RBC): \>=6 Tera/L; Platelets: \<100 Giga/L, \>=700 Giga/L; White blood cells (WBC): \<3.0 Giga/L (Non-Black \[NB\]); \<2.0 Giga/L (Black \[B\]) or \>=16.0 Giga/L; Neutrophils: \<1.5 Giga/L (NB) or \<1.0 Giga/L (B); Lymphocytes: \>4.0 Giga/L; Monocytes: \>0.7 Giga/L; Basophils: \>0.1 Giga/L; Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L). |
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | From first dose of study drug up to 3 days after last administration of study drug (maximum treatment exposure: 192 days) | Criteria for PCSA: Lipase: \>=3 ULN; Amylase: \>=3 ULN; Sodium: \<=129 mmol/L; \>=160 mmol/L; Potassium: \<3 mmol/L, \>=5.5 mmol/L; Creatinine: \>=150 micromoles per liter (umol/L), \>=30% or \>=100% change from baseline; Glomerular filtration rate (GFR): \>=60-\<90 mL/minute(min)/1.73 square meter (m\^2) (mild decrease in GFR), \>=30-\<60 mL/min/1.73m\^2 (moderate decrease in GFR), \>=15-\<30 mL/min/1.73m\^2 (severe decrease in GFR),\<15 mL/min/1.73m\^2 (end stage renal disease); Creatinine clearance (CG): \>=60-\<90 mL/min (mild decrease in GFR), \>=30-\<60 mL/min (moderate decrease in GFR), \>=15-\<30 mL/min (severe decrease in GFR), \<15 mL/min (end stage renal disease); Urea nitrogen (BUN): \>=17 mmol/L and Uric acid: \<120 or \>408 umol/L; Alanine transaminase (ALT) and aspartate transaminase (AST): \>3/5/10/20 ULN. Alkaline phosphatase:\>1.5 ULN, total bilirubin (TBILI): \>1.5 or \>2 ULN, ALT and TBILI:\> ALT\>3ULN and TBILI \>2 ULN and Conjugated and total bilirubin: \>35% TBILI and TBILI \>1.5 ULN. |
| Percentage of Participants Reaching HbA1c <7% at Week 24 With no Clinically Relevant Hypoglycemia During 24-Week Treatment Period | Baseline up to Week 24 | Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c value were considered as non-responders. Participants who reached the specified target of HbA1c without any clinically significant symptoms of hypoglycemia as defined in ADA Levels 2 or 3 are reported. Percentages are rounded off to the tenth decimal place. |
Countries
China
Participant flow
Recruitment details
The study was conducted at 60 centers in China. A total of 733 participants were screened between 07-Jul-2022 and 17-Apr-2023, of which 151 were screen failures. Screen failures were mainly due to not meeting eligibility criteria.
Pre-assignment details
A total of 582 participants were randomized in a 1:1 ratio to receive either insulin glargine/lixisenatide (iGlarLixi) or insulin degludec and insulin aspart (IDegAsp).
Participants by arm
| Arm | Count |
|---|---|
| iGlarLixi Participants self-administered iGlarLixi (100 U/mL insulin glargine + 100 or 50 mcg/mL lixisenatide respectively) SC injection once daily on top of metformin +/- SGLT-2i for 24 weeks. Dose was individually adjusted. | 291 |
| IDegAsp Participants self-administered IDegAsp (100 U/mL of insulin degludec + insulin aspart with a ratio of 70:30) SC injection once daily on top of metformin +/- SGLT-2i for 24 weeks. Dose was individually adjusted. | 291 |
| Total | 582 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Non-compliance with study schedule | 2 | 1 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 13 | 4 |
Baseline characteristics
| Characteristic | iGlarLixi | IDegAsp | Total |
|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 10.2 | 57.5 years STANDARD_DEVIATION 9.9 | 56.9 years STANDARD_DEVIATION 10 |
| Body Mass Index (BMI) | 25.92 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 3.47 | 25.42 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 3.25 | 25.67 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 3.37 |
| Duration of type 2 diabetes | 8.56 years STANDARD_DEVIATION 5.68 | 9.06 years STANDARD_DEVIATION 6 | 8.81 years STANDARD_DEVIATION 5.84 |
| Glycated Hemoglobin (HbA1c) | 8.58 percentage of HbA1c STANDARD_DEVIATION 0.93 | 8.53 percentage of HbA1c STANDARD_DEVIATION 0.9 | 8.55 percentage of HbA1c STANDARD_DEVIATION 0.91 |
| Race/Ethnicity, Customized Asian | 291 Participants | 291 Participants | 582 Participants |
| Randomization stratum of oral antidiabetic (OAD) (s) use at screening Metformin + other OAD | 140 Participants | 140 Participants | 280 Participants |
| Randomization stratum of oral antidiabetic (OAD) (s) use at screening Metformin ± SGLT-2i | 151 Participants | 151 Participants | 302 Participants |
| Randomization stratum of oral antidiabetic (OAD) (s) use at screening Prior use of SGLT-2i | 37 Participants | 37 Participants | 74 Participants |
| Sex: Female, Male Female | 141 Participants | 136 Participants | 277 Participants |
| Sex: Female, Male Male | 150 Participants | 155 Participants | 305 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 290 | 0 / 291 |
| other Total, other adverse events | 152 / 290 | 101 / 291 |
| serious Total, serious adverse events | 15 / 290 | 12 / 291 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 24: Non-Inferiority Analysis
Blood samples were collected at indicated timepoints for analysis of HbA1c. Baseline was defined as the last available pre-dose assessment (on or before Day 1).
Time frame: Baseline, Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| iGlarLixi | Change in HbA1c From Baseline to Week 24: Non-Inferiority Analysis | -1.88 percentage of HbA1c | Standard Error 0.05 |
| IDegAsp | Change in HbA1c From Baseline to Week 24: Non-Inferiority Analysis | -1.68 percentage of HbA1c | Standard Error 0.05 |
Comparison: Statistical analysis for change from baseline in HbA1cp-value: <0.00195% CI: [-0.33, -0.07]ANCOVA
Secondary
Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 24
Participants were provided with a glucometer, corresponding supplies, a leaflet, and with diaries in order to perform self-measurement of plasma glucose and its recording and were trained on how to use the glucometer. The 7-point SMPG profile was measured at the following 7-points: pre-prandial (before starting a meal) and 2 hours postprandial each for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal. The participants performed 7-point SMPG profile measurement over a single 24-hour period on 2 different days in the week. Baseline was defined as the last available pre-dose assessment (on or before Day 1).
Time frame: Baseline, Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| iGlarLixi | Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 24 | -3.36 mmol/L | Standard Error 0.12 |
| IDegAsp | Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 24 | -2.92 mmol/L | Standard Error 0.11 |
Secondary
Change in Body Weight From Baseline to Week 24
Body weight was obtained with the participant wearing undergarments or very light clothing and no shoes, and with an empty bladder. The same scale was used throughout the study. Baseline was defined as the last available pre-dose assessment (on or before Day 1).
Time frame: Baseline, Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| iGlarLixi | Change in Body Weight From Baseline to Week 24 | -0.30 kilogram | Standard Error 0.29 |
| IDegAsp | Change in Body Weight From Baseline to Week 24 | 1.19 kilogram | Standard Error 0.25 |
Comparison: Statistical analysis for change from baseline in body weightp-value: <0.00197.5% CI: [-2.32, -0.66]ANCOVA
Secondary
Change in Fasting C-Peptide From Baseline to Week 24
Blood samples were collected at fasting state (no food or drinks \[except water\] for at least 8 hours) at indicated timepoints. Baseline was defined as the last available pre-dose assessment (on or before Day 1).
Time frame: Baseline, Week 24
Population: Analysis was performed on all randomized participants. Only those participants with data collected at baseline and Week 24 are reported.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| iGlarLixi | Change in Fasting C-Peptide From Baseline to Week 24 | -0.23 nanomoles/liter (nmol/L) | Standard Error 0.02 |
| IDegAsp | Change in Fasting C-Peptide From Baseline to Week 24 | -0.33 nanomoles/liter (nmol/L) | Standard Error 0.02 |
Secondary
Change in Fasting Plasma Glucose From Baseline to Week 24
Blood samples were collected at fasting state (no food or drinks \[except water\] for at least 8 hours) at indicated timepoints. Baseline was defined as the last available pre-dose assessment (on or before Day 1).
Time frame: Baseline, Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| iGlarLixi | Change in Fasting Plasma Glucose From Baseline to Week 24 | -3.18 mmol/L | Standard Error 0.11 |
| IDegAsp | Change in Fasting Plasma Glucose From Baseline to Week 24 | -3.45 mmol/L | Standard Error 0.11 |
Secondary
Change in HbA1c From Baseline to Week 24: Superiority Analysis
Blood samples were collected at indicated timepoints for analysis of HbA1c. Baseline was defined as the last available pre-dose assessment (on or before Day 1).
Time frame: Baseline, Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| iGlarLixi | Change in HbA1c From Baseline to Week 24: Superiority Analysis | -1.88 percentage of HbA1c | Standard Error 0.05 |
| IDegAsp | Change in HbA1c From Baseline to Week 24: Superiority Analysis | -1.68 percentage of HbA1c | Standard Error 0.05 |
Comparison: Statistical analysis for change from baseline in HbA1cp-value: 0.00397.5% CI: [-0.35, -0.05]ANCOVA
Secondary
Hypoglycemic Event Rate During the On-Treatment Period
During the study, participants were instructed to document the presence of hypoglycemic episodes in their study diary. Percentage of hypoglycemic events per participant-year during on-treatment period are reported. The on-treatment period (TE period) was defined as the period from the first injection study treatment to the last injection of study treatment + 3 days (1 day for hypoglycemia).
Time frame: From first dose of study drug up to 1 day after the last administration of study drug (maximum treatment exposure: 192 days)
Population: Analysis was performed on safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iGlarLixi | Hypoglycemic Event Rate During the On-Treatment Period | 1.90 event rate per participant-year |
| IDegAsp | Hypoglycemic Event Rate During the On-Treatment Period | 2.72 event rate per participant-year |
Secondary
Number of Participants With Any Hypoglycemia Event During On-Treatment Period
During the study, participants were instructed to document the presence of hypoglycemic episodes in their study diary. Number of participants who met ADA definition of hypoglycemia during the treatment period are reported. * ADA Level 1 hypoglycemia: A measurable glucose concentration \<70 mg/dL (3.9 mmol/L) but \>=54 mg/dL (3.0 mmol/L). * ADA Level 2 hypoglycemia: Blood glucose concentration \<54mg/dL \[3.0 mmol/L\]; the threshold at which neuroglycopenic symptoms begin to occur and requires immediate action to resolve the hypoglycemic event. * ADA Level 3 hypoglycemia: A severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. The on-treatment period (ie, treatment-emergent \[TE\] period) was defined as the period from the first injection study treatment to the last injection of study treatment + 3 days (1 day for hypoglycemia).
Time frame: From first dose of study drug up to 1 day after the last administration of study drug (maximum treatment exposure: 192 days)
Population: Analysis was performed on safety population which included all randomized participants who had taken at least 1 dose of study intervention, regardless of the amount of treatment administered.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| iGlarLixi | Number of Participants With Any Hypoglycemia Event During On-Treatment Period | 102 Participants |
| IDegAsp | Number of Participants With Any Hypoglycemia Event During On-Treatment Period | 118 Participants |
Secondary
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry
Criteria for PCSA: Lipase: \>=3 ULN; Amylase: \>=3 ULN; Sodium: \<=129 mmol/L; \>=160 mmol/L; Potassium: \<3 mmol/L, \>=5.5 mmol/L; Creatinine: \>=150 micromoles per liter (umol/L), \>=30% or \>=100% change from baseline; Glomerular filtration rate (GFR): \>=60-\<90 mL/minute(min)/1.73 square meter (m\^2) (mild decrease in GFR), \>=30-\<60 mL/min/1.73m\^2 (moderate decrease in GFR), \>=15-\<30 mL/min/1.73m\^2 (severe decrease in GFR),\<15 mL/min/1.73m\^2 (end stage renal disease); Creatinine clearance (CG): \>=60-\<90 mL/min (mild decrease in GFR), \>=30-\<60 mL/min (moderate decrease in GFR), \>=15-\<30 mL/min (severe decrease in GFR), \<15 mL/min (end stage renal disease); Urea nitrogen (BUN): \>=17 mmol/L and Uric acid: \<120 or \>408 umol/L; Alanine transaminase (ALT) and aspartate transaminase (AST): \>3/5/10/20 ULN. Alkaline phosphatase:\>1.5 ULN, total bilirubin (TBILI): \>1.5 or \>2 ULN, ALT and TBILI:\> ALT\>3ULN and TBILI \>2 ULN and Conjugated and total bilirubin: \>35% TBILI and TBILI \>1.5 ULN.
Time frame: From first dose of study drug up to 3 days after last administration of study drug (maximum treatment exposure: 192 days)
Population: Analysis was performed on the safety population. Only those participants with data collected for each parameter during TE period are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Amylase: >=3 ULN | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | BUN: >=17 mmol/L | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | GFR: Mild decrease in GFR | 80 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Uric Acid: <120 umol/L | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Potassium: >=5.5 mmol/L | 1 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Uric Acid: >408 umol/L | 104 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | GFR: Moderate decrease in GFR | 11 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT: >3 ULN | 4 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Sodium: >=160 mmol/L | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT: >5 ULN | 1 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | GFR: Severe decrease in GFR | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT: >10 ULN | 1 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Creatinine: >=150 umol/L | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT: >20 ULN | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | GFR: End stage renal disease | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | AST: >3 ULN | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Sodium: <=129 mmol/L | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | AST: >5 ULN | 1 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | CG: Mild decrease in GFR | 80 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | AST: >10 ULN | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Creatinine: >=30% change from baseline | 36 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | AST: >20 ULN | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | CG: Moderate decrease in GFR | 12 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Alkaline Phosphatase: >1.5 ULN | 2 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Potassium: <3 mmol/L | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | TBILI: >1.5 ULN | 3 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | CG: Severe decrease in GFR | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | TBILI: >2 ULN | 1 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Creatinine: >=100% change from baseline | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT>3ULN and TBILI >2 ULN | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | CG: End stage renal disease | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Conjugated and TBILI: >35% TBILI and TBILI >1.5 ULN | 2 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Lipase: >=3 ULN | 6 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Conjugated and TBILI: >35% TBILI and TBILI >1.5 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Lipase: >=3 ULN | 9 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Amylase: >=3 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Sodium: <=129 mmol/L | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Sodium: >=160 mmol/L | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Potassium: <3 mmol/L | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Potassium: >=5.5 mmol/L | 3 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Creatinine: >=150 umol/L | 1 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Creatinine: >=30% change from baseline | 29 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Creatinine: >=100% change from baseline | 1 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | GFR: Mild decrease in GFR | 79 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | GFR: Moderate decrease in GFR | 11 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | GFR: Severe decrease in GFR | 1 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | GFR: End stage renal disease | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | CG: Mild decrease in GFR | 85 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | CG: Moderate decrease in GFR | 16 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | CG: Severe decrease in GFR | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | CG: End stage renal disease | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | BUN: >=17 mmol/L | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Uric Acid: <120 umol/L | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Uric Acid: >408 umol/L | 108 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT: >3 ULN | 2 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT: >5 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT: >10 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT: >20 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | AST: >3 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | AST: >5 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | AST: >10 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | AST: >20 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | Alkaline Phosphatase: >1.5 ULN | 5 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | TBILI: >1.5 ULN | 1 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | TBILI: >2 ULN | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry | ALT>3ULN and TBILI >2 ULN | 0 Participants |
Secondary
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology
Criteria for PCSA: For Hemoglobin (Hb), there are 3 criteria: (1)\<=115 grams (g)/L (Male\[M\]) or \<=95 g/L (Female\[F\]), (2)\>= 185 g/L (M) or \>=165 g/L (F), and (3) decrease from baseline \>=20 g/L; Hematocrit: \<=0.37 volume/volume (v/v) (M) or \<=0.32 v/v (F), \>=0.55 v/v (M) or \>=0.5 v/v (F); Red blood cells (RBC): \>=6 Tera/L; Platelets: \<100 Giga/L, \>=700 Giga/L; White blood cells (WBC): \<3.0 Giga/L (Non-Black \[NB\]); \<2.0 Giga/L (Black \[B\]) or \>=16.0 Giga/L; Neutrophils: \<1.5 Giga/L (NB) or \<1.0 Giga/L (B); Lymphocytes: \>4.0 Giga/L; Monocytes: \>0.7 Giga/L; Basophils: \>0.1 Giga/L; Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L).
Time frame: From first dose of study drug up to 3 days after last administration of study drug (maximum treatment exposure: 192 days)
Population: Analysis was performed on the safety population. Only those participants with data collected for each parameter during TE period are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | WBC: <3.0 Giga/L (NB); < 2.0 Giga/L (B) | 2 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Monocytes: >0.7 Giga/L | 35 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | RBC: >=6 Tera/L | 5 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Basophils: >0.1 Giga/L | 2 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | WBC: >=16.0 Giga/L | 1 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Eosinophils: >0.5 Giga/L or >ULN | 2 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hb: <=115 g/L (M); <=95 g/L (F) | 4 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Platelets: >=700 Giga/L | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hb: >=185 g/L (M); >=165 g/L (F) | 1 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B) | 5 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hb: Decrease from Baseline >=20 g/L | 25 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Platelets: <100 Giga/L | 3 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Lymphocytes: > 4.0 Giga/L | 4 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hematocrit: >=0.55 v/v (M) or >=0.5 v/v (F) | 37 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hematocrit: <=0.37 v/v (M) or <=0.32 v/v (F) | 2 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hematocrit: >=0.55 v/v (M) or >=0.5 v/v (F) | 30 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Eosinophils: >0.5 Giga/L or >ULN | 2 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | RBC: >=6 Tera/L | 6 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Platelets: <100 Giga/L | 7 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Platelets: >=700 Giga/L | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | WBC: <3.0 Giga/L (NB); < 2.0 Giga/L (B) | 3 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | WBC: >=16.0 Giga/L | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B) | 7 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Lymphocytes: > 4.0 Giga/L | 6 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Monocytes: >0.7 Giga/L | 29 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Basophils: >0.1 Giga/L | 5 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hb: <=115 g/L (M); <=95 g/L (F) | 1 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hb: >=185 g/L (M); >=165 g/L (F) | 4 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hb: Decrease from Baseline >=20 g/L | 19 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology | Hematocrit: <=0.37 v/v (M) or <=0.32 v/v (F) | 6 Participants |
Secondary
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs
Vital signs assessments included systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) in sitting position with their arm outstretched in line with mid-sternum and supported and weight. Criteria for PCSA: SBP: \<=95 millimeters of mercury (mmHg) and decrease from baseline \>=20 mmHg, \>=160 mmHg and increase from baseline \>=20 mmHg; DBP :\<=45 mmHg and decrease from baseline \>=10 mmHg,\>=110 mmHg and increase from baseline \>=10 mmHg; HR: \<=50 beats/min and decrease from baseline \>=20 beats/min,\>=120 beats/min and increase from baseline \>=20 beats/min; Weight \>=5% decrease from baseline, \>=5% increase from baseline.
Time frame: From first dose of study drug up to 3 days after last administration of study drug (maximum treatment exposure: 192 days)
Population: Analysis was performed on the safety population. Only those participants with data collected for each parameter during TE period are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | SBP: <=95 mmHg and decrease from baseline >=20 mmHg | 1 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | SBP: >=160 mmHg and increase from baseline >=20 mmHg | 4 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | DBP :<=45 mmHg and decrease from baseline >=10 mmHg | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | DBP: >=110 mmHg and increase from baseline >=10 mmHg | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | HR: <=50 beats/min and decrease from baseline >=20 beats/min | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | HR: >=120 beats/min and increase from baseline >=20 beats/min | 0 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | Weight: >=5% decrease from baseline | 41 Participants |
| iGlarLixi | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | Weight: >=5% increase from baseline | 29 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | Weight: >=5% increase from baseline | 73 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | SBP: <=95 mmHg and decrease from baseline >=20 mmHg | 1 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | HR: <=50 beats/min and decrease from baseline >=20 beats/min | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | SBP: >=160 mmHg and increase from baseline >=20 mmHg | 7 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | Weight: >=5% decrease from baseline | 19 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | DBP :<=45 mmHg and decrease from baseline >=10 mmHg | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | HR: >=120 beats/min and increase from baseline >=20 beats/min | 0 Participants |
| IDegAsp | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs | DBP: >=110 mmHg and increase from baseline >=10 mmHg | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any adverse event that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was a suspected transmission of any infectious agent via an authorized medicinal product. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. TE period was defined as the period from the first injection study treatment to the last injection of study treatment + 3 days.
Time frame: From signature of the informed consent form up to the final visit regardless of seriousness or relationship to study drug (maximum treatment exposure: 192 days)
Population: Analysis was performed on the safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| iGlarLixi | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation | Any TEAE | 220 Participants |
| iGlarLixi | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation | Any TESAE | 15 Participants |
| iGlarLixi | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation | Any AESI | 6 Participants |
| iGlarLixi | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation | Any TEAE leading to treatment discontinuation | 7 Participants |
| IDegAsp | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation | Any TEAE leading to treatment discontinuation | 1 Participants |
| IDegAsp | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation | Any TEAE | 192 Participants |
| IDegAsp | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation | Any AESI | 2 Participants |
| IDegAsp | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation | Any TESAE | 12 Participants |
Secondary
Percentage of Participants Reaching HbA1c <7% at Week 24
Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c value were considered as non-responders. Percentages are rounded off to the tenth decimal place.
Time frame: Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iGlarLixi | Percentage of Participants Reaching HbA1c <7% at Week 24 | 72.5 percentage of participants |
| IDegAsp | Percentage of Participants Reaching HbA1c <7% at Week 24 | 59.8 percentage of participants |
Comparison: Statistical analysis for percentage of participants reaching HbA1c value \<7% at Week 24p-value: <0.00197.5% CI: [1.25, 2.85]Regression, Logistic
Secondary
Percentage of Participants Reaching HbA1c <7% at Week 24 With no Clinically Relevant Hypoglycemia During 24-Week Treatment Period
Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c value were considered as non-responders. Participants who reached the specified target of HbA1c without any clinically significant symptoms of hypoglycemia as defined in ADA Levels 2 or 3 are reported. Percentages are rounded off to the tenth decimal place.
Time frame: Baseline up to Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iGlarLixi | Percentage of Participants Reaching HbA1c <7% at Week 24 With no Clinically Relevant Hypoglycemia During 24-Week Treatment Period | 66.7 percentage of participants |
| IDegAsp | Percentage of Participants Reaching HbA1c <7% at Week 24 With no Clinically Relevant Hypoglycemia During 24-Week Treatment Period | 56.0 percentage of participants |
Secondary
Percentage of Participants Reaching HbA1c <7% at Week 24 With no Hypoglycemia During 24-Week Treatment Period
Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c value were considered as non-responders. Hypoglycemia was characterized as per ADA 2021 recommendations. * ADA Level 1 hypoglycemia: A measurable glucose concentration \<70 mg/dL (3.9 mmol/L) but \>=54 mg/dL (3.0 mmol/L). * ADA Level 2 hypoglycemia: Blood glucose concentration \<54mg/dL \[3.0 mmol/L\]; the threshold at which neuroglycopenic symptoms begin to occur and requires immediate action to resolve the hypoglycemic event. * ADA Level 3 hypoglycemia: A severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. Percentages are rounded off to the tenth decimal place.
Time frame: Baseline up to Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iGlarLixi | Percentage of Participants Reaching HbA1c <7% at Week 24 With no Hypoglycemia During 24-Week Treatment Period | 43.6 percentage of participants |
| IDegAsp | Percentage of Participants Reaching HbA1c <7% at Week 24 With no Hypoglycemia During 24-Week Treatment Period | 35.7 percentage of participants |
Secondary
Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24
Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c or body weight value were considered as non-responders. Percentages are rounded off to the tenth decimal place.
Time frame: Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iGlarLixi | Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 | 40.5 percentage of participants |
| IDegAsp | Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 | 21.3 percentage of participants |
Comparison: Statistical analysis for percentage of participants reaching HbA1c value \<7% with no body weight gain at Week 24p-value: <0.00195% CI: [1.79, 3.76]Regression, Logistic
Secondary
Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 and no Hypoglycemia During 24-Week Treatment Period
Blood samples were collected at indicated timepoints for analysis of HbA1c. Participants without Week 24 HbA1c or body weight value were considered as non-responders. During the study, participants were instructed to document the presence of hypoglycemic episodes in their study diary. Hypoglycemia was characterized as per American Diabetes Association (ADA) 2021 recommendations. * ADA Level 1 hypoglycemia: A measurable glucose concentration \<70 milligram/deciliter (mg/dL) (3.9 millimoles/liter \[mmol/L\]) but \>=54 mg/dL (3.0 mmol/L). * ADA Level 2 hypoglycemia: Blood glucose concentration \<54 mg/dL \[3.0 mmol/L\]; the threshold at which neuroglycopenic symptoms begin to occur and requires immediate action to resolve the hypoglycemic event. * ADA Level 3 hypoglycemia: A severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery. Percentages are rounded off to the tenth decimal place.
Time frame: Baseline up to Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iGlarLixi | Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 and no Hypoglycemia During 24-Week Treatment Period | 26.5 percentage of participants |
| IDegAsp | Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 and no Hypoglycemia During 24-Week Treatment Period | 13.4 percentage of participants |
Comparison: Statistical analysis for percentage of participants reaching HbA1c value \<7% with no body weight gain at Week 24 and no hypoglycemia during treatmentp-value: <0.00195% CI: [1.52, 3.6]Regression, Logistic
Secondary
Percentage of Participants Who Required Rescue Therapy During the 24-Week Treatment Period
Routine HbA1c value was used to determine the requirement of rescue medication. Threshold value was HbA1c \>8% at Week 12 or later on despite appropriate corrective actions. Percentages are rounded off to the tenth decimal place.
Time frame: Baseline up to Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| iGlarLixi | Percentage of Participants Who Required Rescue Therapy During the 24-Week Treatment Period | 5.2 percentage of participants |
| IDegAsp | Percentage of Participants Who Required Rescue Therapy During the 24-Week Treatment Period | 6.9 percentage of participants |
Secondary
Total Daily Insulin Dose at Week 24
Total daily insulin dose was defined as the sum of the insulin dose from study treatment and non-study treatment (e.g., rescue therapy). It was the average of the last 3 available insulin doses recorded in the electronic case report form in the week before visit.
Time frame: Week 24
Population: Analysis was performed on all randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| iGlarLixi | Total Daily Insulin Dose at Week 24 | 27.68 units | Standard Error 0.84 |
| IDegAsp | Total Daily Insulin Dose at Week 24 | 33.78 units | Standard Error 0.83 |