Comparison of SAR342434 to Humalog as the Rapid Acting Insulin in Adult Patients With Type 2 Diabetes Mellitus Also Using Insulin Glargine

Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data, using all post-baseline HbA1c data available during the 6-month period and adequate contrasts at Week 26.

Time frame: Baseline, Week 26

Population: Analysis was performed on intent-to-treat (ITT) population that included all randomized participants, irrespective of compliance with the study protocol and procedures. Here, number of participants analyzed = participants with at least one post-baseline HbA1c assessment during the 6-month study period.

Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM approach to account for missing data, using all post-baseline FPG data available during the 6-month period and adequate contrasts at Week 26.

Time frame: Baseline, Week 26

Population: Analysis was performed on ITT population. Here, number of participants analyzed = participants with at least one post-baseline FPG assessment during the 6-months study period.

The 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. 7-point SMPGs were performed at least two times in a week before baseline, before visit Week 12 and before visit Week 26. Mean 24-hour plasma glucose concentration was calculated for each profile and then averaged across profiles performed in the week before a visit. Change in mean 24-hour plasma glucose concentration was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during 6-month period and adequate contrasts at Week 26.

Time frame: Baseline, Week 26

Population: Analysis was performed on ITT population. Here, number of participants analyzed = participants with at least one post-baseline mean 24-hour plasma glucose concentration assessment during 6-month study period.

Plasma glucose excursions were calculated at breakfast, lunch and dinner for each 7-point SMPG profile, as 2-hour postprandial glucose (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 average across the profiles performed in the week before the visit. Change in PPG excursions was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during the 6-month period and adequate contrasts at Week 26.

Time frame: Baseline, Week 26

Population: Analysis was performed on ITT population. Here, number analyzed in each row = participants with at least one post-baseline data during the 6-month period for specified categories.

Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.

Time frame: Week 26

Population: Analysis was performed on ITT population.

Percentage of participants with hypersensitivity reactions and injection site reactions were reported.

Time frame: First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Population: Analysis was performed on safety population.

Percentage of participants with at least one treatment emergent hypoglycemia reported at any time of the day 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. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=70 mg/dL (3.9 mmol/L). Hypoglycemic episodes with plasma glucose of 54 mg/dL (\<3.0 mmol/L) were also analyzed.

Time frame: First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Population: Analysis was performed on safety population that included all participants randomized and exposed to at least 1 dose of investigational medicinal product (IMP) (SAR342434 or Humalog), regardless of the amount of treatment administered.

Participants with treatment-emergent AIA (incidence) were reported (as participants with treatment-boosted or treatment-induced AIAs). Participants with treatment-induced AIAs were participants 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). Participants with treatment-boosted AIAs were participants 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, in those participants with pre-existing AIA).

Time frame: First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 210 days)

Population: Analysis was performed on anti-insulin antibody population that included all participants from the safety population with at least one AIA sample available for analysis during the 6-months on-treatment period.

Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Week 26 value.

Time frame: Baseline, Week 26

Population: Analysis was performed on safety population. Here, number analyzed in each row = participants with available data for specified categories.