Trial Outcomes & Findings for Comparison of SAR341402 to NovoLog/NovoRapid in Adult Patients With Diabetes Mellitus Also Using Insulin Glargine (NCT NCT03211858)

Last Updated: 2022-03-28

Results Overview

All values up to Week 26 were taken into account in the analysis, regardless of adherence to treatment. Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Missing changes at Week 26 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted least square (LS) means and standard errors (SE) were obtained using an analysis of covariance (ANCOVA) model on data obtained from the multiple imputations (results were combined using Rubin's formulae).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

597 participants

Primary outcome timeframe

Baseline, Week 26

Results posted on

2022-03-28

Participant Flow

The study was conducted at 82 centers in 7 countries. A total of 846 participants were screened between 02 August 2017 and 29 December 2017, of which 249 participants were screen failures. Screen failures were mainly due to glycated hemoglobin A1c (HbA1c) level lesser than (\<) 7.0% or greater than (\>) 10% at the screening visit.

Randomization was stratified by HbA1c at screening visit (\<8%, greater than or equal to \[\>=\] 8%), prior use of NovoLog/NovoRapid (Yes, No), geographical region (Europe, United States \[US\], Japan) and type 1 or 2 of diabetes mellitus (T1DM/T2DM \[US only\]). Assigned to arms in 1:1 ratio (SAR341402: NovoLog/NovoRapid).

Participant milestones

Participant milestones
Measure	SAR341402 SAR341402 100 units per milliliter (U/mL) subcutaneous (SC) injection, before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.	NovoLog/NovoRapid NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine,up to Week 52.
Overall Study STARTED	301	296
Overall Study Treated	301	296
Overall Study COMPLETED	264	263
Overall Study NOT COMPLETED	37	33

Reasons for withdrawal

Reasons for withdrawal
Measure	SAR341402 SAR341402 100 units per milliliter (U/mL) subcutaneous (SC) injection, before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.	NovoLog/NovoRapid NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine,up to Week 52.
Overall Study Adverse Event	8	6
Overall Study Lack of Efficacy	0	4
Overall Study Poor compliance to protocol	6	2
Overall Study Non-serious Hypoglycemia	1	0
Overall Study Other than specified above	22	21

Baseline Characteristics

Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Total n=597 Participants Total of all reporting groups
Age, Continuous	48.4 years STANDARD_DEVIATION 14.8 • n=301 Participants	47.8 years STANDARD_DEVIATION 15.4 • n=296 Participants	48.1 years STANDARD_DEVIATION 15.1 • n=597 Participants
Sex: Female, Male Female	122 Participants n=301 Participants	119 Participants n=296 Participants	241 Participants n=597 Participants
Sex: Female, Male Male	179 Participants n=301 Participants	177 Participants n=296 Participants	356 Participants n=597 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=300 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	2 Participants n=293 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	2 Participants n=593 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.
Race (NIH/OMB) Asian	37 Participants n=300 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	37 Participants n=293 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	74 Participants n=593 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=300 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	0 Participants n=293 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	3 Participants n=593 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.
Race (NIH/OMB) Black or African American	11 Participants n=300 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	8 Participants n=293 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	19 Participants n=593 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.
Race (NIH/OMB) White	248 Participants n=300 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	242 Participants n=293 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	490 Participants n=593 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.
Race (NIH/OMB) More than one race	0 Participants n=300 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	3 Participants n=293 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	3 Participants n=593 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=300 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	1 Participants n=293 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.	2 Participants n=593 Participants • Here, "Overall number of participants analyzed" = participants evaluable for this baseline measure.
Baseline Body Mass Index (BMI)	27.45 kilogram/meter square^2 (kg/m^2) STANDARD_DEVIATION 4.58 • n=301 Participants	27.46 kilogram/meter square^2 (kg/m^2) STANDARD_DEVIATION 4.99 • n=296 Participants	27.45 kilogram/meter square^2 (kg/m^2) STANDARD_DEVIATION 4.78 • n=597 Participants
Duration of Diabetes	19.5 years STANDARD_DEVIATION 11.9 • n=301 Participants	19.4 years STANDARD_DEVIATION 11.8 • n=296 Participants	19.5 years STANDARD_DEVIATION 11.8 • n=597 Participants
Glycated Haemoglobin	8.00 percentage of hemoglobin STANDARD_DEVIATION 0.77 • n=301 Participants	7.94 percentage of hemoglobin STANDARD_DEVIATION 0.70 • n=296 Participants	7.97 percentage of hemoglobin STANDARD_DEVIATION 0.74 • n=597 Participants
Randomization Strata of Types of Diabetes Type 1 Diabetes Mellitus	250 Participants n=301 Participants	247 Participants n=296 Participants	497 Participants n=597 Participants
Randomization Strata of Types of Diabetes Type 2 Diabetes Mellitus	51 Participants n=301 Participants	49 Participants n=296 Participants	100 Participants n=597 Participants
Randomization Strata of Screening HbA1c Categories HbA1c <8%	143 Participants n=301 Participants	138 Participants n=296 Participants	281 Participants n=597 Participants
Randomization Strata of Screening HbA1c Categories HbA1c >=8%	158 Participants n=301 Participants	158 Participants n=296 Participants	316 Participants n=597 Participants
Randomization Strata of Prior Use of NovoLog/NovoRapid No (Humalog/Liprolog)	109 Participants n=301 Participants	108 Participants n=296 Participants	217 Participants n=597 Participants
Randomization Strata of Prior Use of NovoLog/NovoRapid Yes (NovoLog/NovoRapid)	192 Participants n=301 Participants	188 Participants n=296 Participants	380 Participants n=597 Participants
Randomization strata of geographical region Europe	98 Participants n=301 Participants	99 Participants n=296 Participants	197 Participants n=597 Participants
Randomization strata of geographical region Japan	33 Participants n=301 Participants	32 Participants n=296 Participants	65 Participants n=597 Participants
Randomization strata of geographical region US	170 Participants n=301 Participants	165 Participants n=296 Participants	335 Participants n=597 Participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: Analysis was performed on intent-to-treat (ITT) population, which included all randomized participants, irrespective of compliance with the study protocol and procedures.

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Change in Glycated Hemoglobin A1c (HbA1c) From Baseline to Week 26	-0.38 percentage of HbA1c Standard Error 0.042	-0.30 percentage of HbA1c Standard Error 0.041	—	—

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Analysis was performed on ITT population.

All values up to Week 52 were taken into account in the analysis, regardless of adherence to treatment. Change in HbA1c was calculated by subtracting baseline value from Week 52 value. Missing changes at Week 52 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted LS means and SE were obtained using ANCOVA model on data obtained from the multiple imputations (results were combined using Rubin's formulae).

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Change in HbA1c From Baseline to Week 52	-0.25 percentage of HbA1c Standard Error 0.057	-0.26 percentage of HbA1c Standard Error 0.059	—	—

SECONDARY outcome

Timeframe: Week 26 and Week 52

Population: Analysis was performed on ITT population.

Participants who had no available assessment at Week 26 and Week 52 were considered as non-responders.

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Percentage of Participants With HbA1c <7% at Week 26 and Week 52 At Week 26	16.6 percentage of participants	14.5 percentage of participants	—	—
Percentage of Participants With HbA1c <7% at Week 26 and Week 52 At Week 52	19.6 percentage of participants	18.2 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26, and Week 52

Population: Analysis was performed on ITT population.

All values up to Week 26 and Week 52 were taken into account in the analysis, regardless of adherence to treatment. Change in FPG at Week 26 and 52 was calculated by subtracting baseline value from Week 26 and Week 52 values, respectively. Missing changes at Week 26 and Week 52 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted LS means and SE were obtained using ANCOVA analysis on data obtained from the multiple imputations (results were combined using Rubin's formulae).

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 and Week 52 At Week 26	-0.49 millimoles per liter (mmol/L) Standard Error 0.249	-0.17 millimoles per liter (mmol/L) Standard Error 0.245	—	—
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 and Week 52 At Week 52	-0.10 millimoles per liter (mmol/L) Standard Error 0.366	-0.34 millimoles per liter (mmol/L) Standard Error 0.359	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26, and Week 52

Population: Analysis was performed on ITT population. Here, "Overall number of participants analyzed" = participants with a baseline mean 24-hour plasma glucose concentration.

Mean 24-hour plasma glucose concentration was calculated based on 7-point self-measured plasma glucose (SMPG) profiles with plasma glucose measurements before and 2-hours after each main meal and at bedtime. Mean 24-hour plasma glucose concentration was calculated for each profile and then averaged across profiles performed in the week before a visit. All calculated values up to Week 26 and Week 52 were taken into account in the analysis, regardless of adherence to treatment. Change in mean 24-hour plasma glucose concentration at Weeks 26 and 52 was calculated by subtracting baseline value from Week 26 and Week 52 values, respectively. Missing changes at Week 26 and Week 52 were imputed using a return-to-baseline multiple imputation method (values imputed as participant baseline plus an error). Adjusted LS means and SE were obtained using ANCOVA analysis on data obtained from the multiple imputations (results were combined using Rubin's formulae).

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=295 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Change in the Mean 24-hour Plasma Glucose Concentration From Baseline to Week 26 and Week 52 At Week 26	-0.34 mmol/L Standard Error 0.120	-0.53 mmol/L Standard Error 0.121	—	—
Change in the Mean 24-hour Plasma Glucose Concentration From Baseline to Week 26 and Week 52 At Week 52	0.12 mmol/L Standard Error 0.144	-0.18 mmol/L Standard Error 0.147	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26, and Week 52

Population: Analysis was performed on ITT population. Here, "Number analyzed" = participants with a baseline value for each specified category.

Plasma glucose excursions were calculated at breakfast, lunch and dinner for each 7-point SMPG profile, as 2-hour PPG minus plasma glucose value obtained 30 minutes prior to start of the meal. Values of plasma glucose excursions at each visit were then calculated as the average across profiles performed in the week before the visit. All calculated values up to Week 26 and Week 52 were taken into account in the analysis, regardless of adherence to treatment. Change in PPG excursions at Weeks 26 and 52 was calculated by subtracting baseline value from Week 26 and Week 52 values, respectively. Missing changes at Week 26 and Week 52 were imputed using a return-to-baseline multiple imputation method (values imputed as participant baseline plus an error). Adjusted LS means and SE were obtained using ANCOVA analysis on data obtained from the multiple imputations (results were combined using Rubin's formulae).

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 and Week 52 Week 26: At Breakfast	0.50 mmol/L Standard Error 0.232	0.65 mmol/L Standard Error 0.233	—	—
Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 and Week 52 Week 26: At Lunch	0.18 mmol/L Standard Error 0.230	0.12 mmol/L Standard Error 0.228	—	—
Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 and Week 52 Week 26: At Dinner	0.36 mmol/L Standard Error 0.243	0.66 mmol/L Standard Error 0.243	—	—
Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 and Week 52 Week 52: At Breakfast	0.73 mmol/L Standard Error 0.253	0.91 mmol/L Standard Error 0.255	—	—
Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 and Week 52 Week 52: At Lunch	0.43 mmol/L Standard Error 0.252	0.34 mmol/L Standard Error 0.251	—	—
Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 and Week 52 Week 52: At Dinner	0.26 mmol/L Standard Error 0.255	0.51 mmol/L Standard Error 0.254	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26, and Week 52

Population: Analysis was performed on ITT population. Here, "Number analyzed" = participants with an available value at baseline, Week 26/Week 52 for the specified 7-point SMPG time point.

7-point SMPG profiles were measured at the following 7 points at each visit (Baseline, Week 26, and Week 52): before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, and bedtime. For each time point, the value at each visit was calculated as the average of values obtained for the same time point across profiles performed in the week before the visit.

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 26: Before Breakfast	-0.62 mmol/L Standard Deviation 4.48	-0.50 mmol/L Standard Deviation 3.98	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 26: 2 Hours After Breakfast	-0.39 mmol/L Standard Deviation 4.97	-0.30 mmol/L Standard Deviation 4.12	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 26: Before Lunch	-0.60 mmol/L Standard Deviation 4.14	-0.60 mmol/L Standard Deviation 4.25	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 26: 2 Hours After Lunch	-0.61 mmol/L Standard Deviation 4.54	-0.62 mmol/L Standard Deviation 4.65	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 26: Before Dinner	-0.04 mmol/L Standard Deviation 4.87	-0.78 mmol/L Standard Deviation 4.12	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 26: 2 Hours After Dinner	-0.36 mmol/L Standard Deviation 4.71	-0.25 mmol/L Standard Deviation 4.14	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 26: Bedtime	-0.71 mmol/L Standard Deviation 5.13	-0.54 mmol/L Standard Deviation 4.03	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 52: Before Breakfast	-0.54 mmol/L Standard Deviation 4.80	-0.31 mmol/L Standard Deviation 4.37	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 52: 2 Hours After Breakfast	-0.21 mmol/L Standard Deviation 4.30	0.05 mmol/L Standard Deviation 4.31	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 52: Before Lunch	0.24 mmol/L Standard Deviation 4.64	-0.13 mmol/L Standard Deviation 4.24	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 52: 2 Hours After Lunch	0.05 mmol/L Standard Deviation 5.01	-0.37 mmol/L Standard Deviation 4.64	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 52: Before Dinner	0.75 mmol/L Standard Deviation 5.59	-0.06 mmol/L Standard Deviation 4.26	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 52: 2 Hours After Dinner	0.16 mmol/L Standard Deviation 4.60	-0.17 mmol/L Standard Deviation 4.63	—	—
Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point Week 52: Bedtime	-0.11 mmol/L Standard Deviation 4.98	0.10 mmol/L Standard Deviation 4.30	—	—

SECONDARY outcome

Timeframe: From first injection of investigational medicinal product (IMP) up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier, for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52

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

Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=3.9 mmol/L (\<=70 mg/dL) or plasma glucose level of \<3.0 mmol/L (\<54 mg/dL).

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Number of Participants With at Least One Hypoglycemic Event Week 52: Any hypoglycemia	295 Participants	290 Participants	—	—
Number of Participants With at Least One Hypoglycemic Event Week 52: Documented symptomatic <=3.9 mmol/L	274 Participants	267 Participants	—	—
Number of Participants With at Least One Hypoglycemic Event Week 26: Any hypoglycemia	291 Participants	285 Participants	—	—
Number of Participants With at Least One Hypoglycemic Event Week 26: Severe hypoglycemia	12 Participants	10 Participants	—	—
Number of Participants With at Least One Hypoglycemic Event Week 26: Documented symptomatic <=3.9 mmol/L	264 Participants	251 Participants	—	—
Number of Participants With at Least One Hypoglycemic Event Week 26: Documented symptomatic < 3.0 mmol/L	207 Participants	193 Participants	—	—
Number of Participants With at Least One Hypoglycemic Event Week 52: Severe hypoglycemia	18 Participants	14 Participants	—	—
Number of Participants With at Least One Hypoglycemic Event Week 52: Documented symptomatic hypo < 3.0 mmol/L	223 Participants	220 Participants	—	—

SECONDARY outcome

Population: Analysis was performed on safety population.

Number of hypoglycemia events (any, severe and documented \[both thresholds\]) per participant-year of exposure were reported. Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because the participant was not capable of helping self. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=3.9 mmol/L (\<=70 mg/dL) or plasma glucose level of \<3.0 mmol/L (\<54 mg/dL).

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Number of Hypoglycemia Events Per Participant-Year Week 52: Severe hypo	0.12 events per participant-year	0.08 events per participant-year	—	—
Number of Hypoglycemia Events Per Participant-Year Week 26: Any hypo	73.33 events per participant-year	69.71 events per participant-year	—	—
Number of Hypoglycemia Events Per Participant-Year Week 26: Severe hypo	0.14 events per participant-year	0.10 events per participant-year	—	—
Number of Hypoglycemia Events Per Participant-Year Week 26:Documented symptomatic hypo (<=3.9 mmol/L)	40.36 events per participant-year	36.37 events per participant-year	—	—
Number of Hypoglycemia Events Per Participant-Year Week 26: Documented symptomatic hypo (<3.0 mmol/L)	11.18 events per participant-year	9.81 events per participant-year	—	—
Number of Hypoglycemia Events Per Participant-Year Week 52: Any hypo	66.00 events per participant-year	64.46 events per participant-year	—	—
Number of Hypoglycemia Events Per Participant-Year Week 52:Documented symptomatic hypo (<=3.9 mmol/L)	35.68 events per participant-year	33.73 events per participant-year	—	—
Number of Hypoglycemia Events Per Participant-Year Week 52: Documented symptomatic hypo (<3.0 mmol/L)	9.37 events per participant-year	8.91 events per participant-year	—	—

SECONDARY outcome

Timeframe: From first injection of IMP up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier, for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52

Population: Analysis was performed on safety population.

Participants with at least one treatment-emergent adverse event linked to hypersensitivity reaction and injection site reaction regardless of relationship to IMP during the main 6-month and the 12-month on-treatment periods was assessed and reported.

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions Week 26: Hypersensitivity Reactions	3.7 percentage of participants	3.7 percentage of participants	—	—
Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions Week 26: Injection site reactions	0.7 percentage of participants	1.4 percentage of participants	—	—
Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions Week 52: Hypersensitivity Reactions	5.6 percentage of participants	7.1 percentage of participants	—	—
Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions Week 52: Injection site reactions	0.7 percentage of participants	1.4 percentage of participants	—	—

SECONDARY outcome

Population: Analysis was performed on AIA population, which included all participants who received at least one dose of IMP and had at least one AIA sample available for analysis during the on-treatment period, analyzed according to the treatment actually received. Here, "Number analyzed" = participants included in the AIA population at Week 26 and Week 52.

Participants with at least one positive AIA sample at baseline or at any time during the on-treatment period (Prevalence).

Outcome measures

Outcome measures
Measure	SAR341402 n=298 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=292 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Percentage of Participants With at Least One Positive Anti-Insulin Aspart Antibodies (AIA) Sample At Week 26	48.0 percentage of participants	52.4 percentage of participants	—	—
Percentage of Participants With at Least One Positive Anti-Insulin Aspart Antibodies (AIA) Sample At Week 52	54.7 percentage of participants	58.2 percentage of participants	—	—

SECONDARY outcome

Population: Analysis was performed on AIA population. Here, 'Number analyzed' = participants included in the AIA population at Week 26 and Week 52 and with negative or missing AIA status at baseline (for treatment-induced AIA) or with positive AIA status at baseline (for treatment-boosted AIA).

AIA incidence were categorized as: treatment-induced, treatment-boosted AIAs, and treatment-emergent AIA. 1) Participants with treatment-induced AIAs were those who developed AIA following IMP administration (participants with at least one positive AIA sample at any time during on-treatment period, in those participants without pre-existing AIA or with missing baseline sample). 2) Participants with treatment-boosted AIAs were those with pre-existing AIAs that were boosted to a significant higher titer following IMP administration (participants with at least one AIA sample with at least a 4-fold increase in titers compared to baseline value at any time during on-treatment period). 3) Participants with treatment-emergent AIA were defined as participants with treatment-induced, or treatment-boosted AIAs.

Outcome measures

Outcome measures
Measure	SAR341402 n=298 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=292 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs) Week 26: Treatment-Induced AIA	23.0 percentage of participants	28.4 percentage of participants	—	—
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs) Week 26: Treatment-Boosted AIA	4.2 percentage of participants	5.1 percentage of participants	—	—
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs) Week 26: Treatment-Emergent AIA	16.9 percentage of participants	20.5 percentage of participants	—	—
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs) Week 52: Treatment-Induced AIA	33.2 percentage of participants	37.1 percentage of participants	—	—
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs) Week 52: Treatment-Boosted AIA	9.4 percentage of participants	13.3 percentage of participants	—	—
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs) Week 52: Treatment-Emergent AIA	25.5 percentage of participants	29.1 percentage of participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 26 and Week 52

Population: Analysis was performed on ITT population and data was summarized separately for each treatment arm in each subgroup (based on the prior use of NovoLog/NovoRapid or Humalog/Liprolog).

All values up to Week 26 and Week 52 were taken into account in the analysis, regardless of adherence to treatment. Change in HbA1c at Week 26 and Week 52 was calculated by subtracting baseline value from Week 26 and Week 52 value, respectively. Missing changes at Week 26 and Week 52 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted LS means and SE were obtained using ANCOVA model on data obtained from the multiple imputations (results were combined using Rubin's formulae).

Outcome measures

Outcome measures
Measure	SAR341402 n=192 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=188 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 n=109 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid n=108 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Change in Glycated Hemoglobin A1c From Baseline to Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog At Week 26	-0.37 percentage of HbA1c Standard Error 0.052	-0.33 percentage of HbA1c Standard Error 0.052	-0.39 percentage of HbA1c Standard Error 0.070	-0.24 percentage of HbA1c Standard Error 0.067
Change in Glycated Hemoglobin A1c From Baseline to Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog At Week 52	-0.28 percentage of HbA1c Standard Error 0.065	-0.26 percentage of HbA1c Standard Error 0.069	-0.19 percentage of HbA1c Standard Error 0.091	-0.26 percentage of HbA1c Standard Error 0.087

OTHER_PRE_SPECIFIED outcome

Population: Analysis was performed on safety population and data was summarized separately for each treatment arm in each subgroup (based on the prior use of NovoLog/NovoRapid or Humalog/Liprolog).

Outcome measures

Outcome measures
Measure	SAR341402 n=192 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=188 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 n=109 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid n=108 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 26: Any hypoglycemia	187 Participants	179 Participants	104 Participants	106 Participants
Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 26: Severe hypoglycemia	6 Participants	7 Participants	6 Participants	3 Participants
Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 26: Documented symptomatic <=3.9 mmol/L	170 Participants	162 Participants	94 Participants	89 Participants
Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 26: Documented symptomatic < 3.0 mmol/L	139 Participants	123 Participants	67 Participants	70 Participants
Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 52: Any hypoglycemia	190 Participants	184 Participants	105 Participants	106 Participants
Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 52: Severe hypoglycemia	10 Participants	9 Participants	8 Participants	5 Participants
Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 52: Documented symptomatic <=3.9 mmol/L	175 Participants	171 Participants	99 Participants	96 Participants
Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 52: Documented symptomatic < 3.0 mmol/L	149 Participants	138 Participants	74 Participants	82 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From first injection of IMP up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52

Population: Analysis was performed on safety population and data was summarized separately for each treatment arm in each subgroup (based on the prior use of NovoLog/NovoRapid or Humalog/Liprolog).

Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during the main 6-month or 12-month on-treatment periods.

Outcome measures

Outcome measures
Measure	SAR341402 n=192 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=188 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 n=109 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid n=108 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Number of Participants With Adverse Events: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 52: Any TEAE	115 Participants	109 Participants	69 Participants	59 Participants
Number of Participants With Adverse Events: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 26: Any TEAE	92 Participants	94 Participants	64 Participants	52 Participants

OTHER_PRE_SPECIFIED outcome

AIA incidence were categorized as: treatment-induced, treatment-boosted AIAs, and treatment-emergent AIA. 1) Participants with treatment-induced AIAs were those who developed AIA following IMP administration (participants with at least one positive AIA sample at any time during on-treatment period, in those participants without pre-existing AIA or with missing baseline sample. 2) Participants with treatment-boosted AIAs were those with pre-existing AIAs that were boosted to a significant higher titer following IMP administration (participants with at least one AIA sample with at least a 4-fold increase in titers compared to baseline value at any time during on-treatment period). 3) Participants with treatment-emergent AIA were defined as participants with treatment-induced, or treatment-boosted AIAs. Data was summarized separately for each treatment arm in each subgroup (based on the prior use of NovoLog/NovoRapid or Humalog/Liprolog).

Outcome measures

Outcome measures
Measure	SAR341402 n=191 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=185 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 n=107 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid n=107 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs): Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 26: Treatment-Induced AIA	18.7 percentage of participants	28.3 percentage of participants	29.9 percentage of participants	28.4 percentage of participants
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs): Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 26: Treatment-Boosted AIA	1.5 percentage of participants	4.6 percentage of participants	10.7 percentage of participants	6.1 percentage of participants
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs): Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 26: Treatment-Emergent AIA	12.6 percentage of participants	20.0 percentage of participants	24.8 percentage of participants	21.5 percentage of participants
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs): Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 52: Treatment-Induced AIA	30.1 percentage of participants	34.2 percentage of participants	38.0 percentage of participants	41.9 percentage of participants
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs): Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 52: Treatment-Boosted AIA	5.9 percentage of participants	15.4 percentage of participants	17.9 percentage of participants	9.1 percentage of participants
Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs): Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Week 52: Treatment-Emergent AIA	21.5 percentage of participants	27.6 percentage of participants	32.7 percentage of participants	31.8 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 1, Week 26 and Week 52

Population: Analysis was performed on safety population. Here, 'Number analyzed' = participants with available data for each specified category.

Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Day1, Week 26 and Week 52 values respectively. Baseline was defined as the median of daily doses available in the week prior to the first injection of IMP (corresponding to doses of the pre-study insulin), value at Day 1 as the median of daily doses available in the week after the first injection of IMP (first doses of IMP), and value at Week 26 and Week 52 as the median of daily doses available in the week prior to each visit.

Outcome measures

Outcome measures
Measure	SAR341402 n=301 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52 Basal insulin dose at Day 1	-0.004 Units/kilogram (U/kg) Standard Deviation 0.036	-0.000 Units/kilogram (U/kg) Standard Deviation 0.023	—	—
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52 Mealtime insulin dose at Day 1	0.003 Units/kilogram (U/kg) Standard Deviation 0.074	0.003 Units/kilogram (U/kg) Standard Deviation 0.091	—	—
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52 Total insulin dose at Day 1	-0.001 Units/kilogram (U/kg) Standard Deviation 0.076	0.002 Units/kilogram (U/kg) Standard Deviation 0.090	—	—
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52 Basal insulin dose at Week 26	0.005 Units/kilogram (U/kg) Standard Deviation 0.081	0.003 Units/kilogram (U/kg) Standard Deviation 0.088	—	—
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52 Mealtime insulin dose at Week 26	-0.011 Units/kilogram (U/kg) Standard Deviation 0.133	0.011 Units/kilogram (U/kg) Standard Deviation 0.116	—	—
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52 Total insulin dose at Week 26	-0.007 Units/kilogram (U/kg) Standard Deviation 0.167	0.015 Units/kilogram (U/kg) Standard Deviation 0.170	—	—
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52 Basal insulin dose at Week 52	0.006 Units/kilogram (U/kg) Standard Deviation 0.085	0.005 Units/kilogram (U/kg) Standard Deviation 0.095	—	—
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52 Mealtime insulin dose at Week 52	-0.001 Units/kilogram (U/kg) Standard Deviation 0.152	0.009 Units/kilogram (U/kg) Standard Deviation 0.123	—	—
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52 Total insulin dose at Week 52	0.005 Units/kilogram (U/kg) Standard Deviation 0.175	0.013 Units/kilogram (U/kg) Standard Deviation 0.165	—	—

POST_HOC outcome

Timeframe: Baseline, Day 1, Week 26, Week 52

Population: Analysis was performed on safety population and data was summarized separately for each treatment arm in each subgroup (based on the prior use of NovoLog/NovoRapid or Humalog/Liprolog). Here, 'Number analyzed' = participants with available data for each specified category.

Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Day 1, Week 26 and Week 52 values respectively. Baseline was defined as the median of daily doses available in the week prior to the first injection of IMP (corresponding to doses of the pre-study insulin), value at Day 1 as the median of daily doses available in the week after the first injection of IMP (first doses of IMP), and value at Week 26 and Week 52 as the median of daily doses available in the week prior to each visit.

Outcome measures

Outcome measures
Measure	SAR341402 n=192 Participants SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=188 Participants NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: SAR341402 n=109 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	Prior Humalog/Liprolog Use: NovoLog/NovoRapid n=108 Participants Participants with prior use of Humalog/Liprolog (as per randomization stratum), receiving NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Basal insulin dose at Day 1	-0.005 U/kg Standard Deviation 0.037	0.0000 U/kg Standard Deviation 0.021	-0.002 U/kg Standard Deviation 0.033	-0.002 U/kg Standard Deviation 0.026
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Mealtime insulin dose at Day 1	-0.000 U/kg Standard Deviation 0.073	-0.003 U/kg Standard Deviation 0.071	0.008 U/kg Standard Deviation 0.075	0.013 U/kg Standard Deviation 0.118
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Total insulin dose at Day 1	-0.006 U/kg Standard Deviation 0.075	-0.003 U/kg Standard Deviation 0.077	0.006 U/kg Standard Deviation 0.079	0.011 U/kg Standard Deviation 0.111
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Basal insulin dose at Week 26	0.003 U/kg Standard Deviation 0.087	0.009 U/kg Standard Deviation 0.065	0.008 U/kg Standard Deviation 0.070	-0.006 U/kg Standard Deviation 0.118
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Mealtime insulin dose at Week 26	-0.009 U/kg Standard Deviation 0.133	0.019 U/kg Standard Deviation 0.114	-0.015 U/kg Standard Deviation 0.133	-0.003 U/kg Standard Deviation 0.121
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Total insulin dose at Week 26	-0.007 U/kg Standard Deviation 0.171	0.027 U/kg Standard Deviation 0.142	-0.008 U/kg Standard Deviation 0.159	-0.006 U/kg Standard Deviation 0.210
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Basal insulin dose at Week 52	0.004 U/kg Standard Deviation 0.094	0.013 U/kg Standard Deviation 0.088	0.010 U/kg Standard Deviation 0.067	-0.009 U/kg Standard Deviation 0.105
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Mealtime insulin dose at Week 52	-0.000 U/kg Standard Deviation 0.156	0.015 U/kg Standard Deviation 0.132	-0.001 U/kg Standard Deviation 0.147	-0.001 U/kg Standard Deviation 0.105
Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog Total insulin dose at Week 52	0.003 U/kg Standard Deviation 0.177	0.025 U/kg Standard Deviation 0.169	0.009 U/kg Standard Deviation 0.171	-0.009 U/kg Standard Deviation 0.156

Adverse Events

SAR341402

Serious events: 36 serious events

Other events: 70 other events

Deaths: 1 deaths

NovoLog/NovoRapid

Serious events: 29 serious events

Other events: 66 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	SAR341402 n=301 participants at risk SAR341402 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.	NovoLog/NovoRapid n=296 participants at risk NovoLog/NovoRapid 100 U/mL SC injection, before meals intake on top of QD Insulin Glargine, up to Week 52.
Infections and infestations Influenza	5.0% 15/301 • Number of events 15 • All Adverse Events (AEs) weeks were collected from signature of the informed consent form up to the study completion (up to 52 Weeks) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent AEs, that is AEs that developed/worsened or became serious and deaths that occurred during the '12-month on-treatment period' (time from the first injection of IMP up to 1 day after the last injection of IMP). Analysis was performed on safety population.	4.1% 12/296 • Number of events 13 • All Adverse Events (AEs) weeks were collected from signature of the informed consent form up to the study completion (up to 52 Weeks) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent AEs, that is AEs that developed/worsened or became serious and deaths that occurred during the '12-month on-treatment period' (time from the first injection of IMP up to 1 day after the last injection of IMP). Analysis was performed on safety population.
Infections and infestations Nasopharyngitis	11.3% 34/301 • Number of events 45 • All Adverse Events (AEs) weeks were collected from signature of the informed consent form up to the study completion (up to 52 Weeks) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent AEs, that is AEs that developed/worsened or became serious and deaths that occurred during the '12-month on-treatment period' (time from the first injection of IMP up to 1 day after the last injection of IMP). Analysis was performed on safety population.	9.8% 29/296 • Number of events 39 • All Adverse Events (AEs) weeks were collected from signature of the informed consent form up to the study completion (up to 52 Weeks) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent AEs, that is AEs that developed/worsened or became serious and deaths that occurred during the '12-month on-treatment period' (time from the first injection of IMP up to 1 day after the last injection of IMP). Analysis was performed on safety population.
Infections and infestations Upper Respiratory Tract Infection	7.3% 22/301 • Number of events 28 • All Adverse Events (AEs) weeks were collected from signature of the informed consent form up to the study completion (up to 52 Weeks) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent AEs, that is AEs that developed/worsened or became serious and deaths that occurred during the '12-month on-treatment period' (time from the first injection of IMP up to 1 day after the last injection of IMP). Analysis was performed on safety population.	9.5% 28/296 • Number of events 31 • All Adverse Events (AEs) weeks were collected from signature of the informed consent form up to the study completion (up to 52 Weeks) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are treatment-emergent AEs, that is AEs that developed/worsened or became serious and deaths that occurred during the '12-month on-treatment period' (time from the first injection of IMP up to 1 day after the last injection of IMP). Analysis was performed on safety population.

Additional Information

Trial Transparency Team

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER