Trial Outcomes & Findings for Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination Compared to Insulin Glargine Alone and Lixisenatide Alone on Top of Metformin in Patients With T2DM (NCT NCT02058147)

NCT ID: NCT02058147

Last Updated: 2017-05-09

Results Overview

Primary outcome was to test superiority of FRC versus Lixisenatide and non-inferiority versus Insulin glargine. Change in HbA1c was calculated by subtracting baseline value from Week 30 value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1170 participants

Primary outcome timeframe

Baseline, Week 30

Results posted on

2017-05-09

Participant Flow

The study was conducted at 240 centers in 23 countries. A total of 2457 participants were screened between February 12, 2014 and September 16, 2014. 978 participants were not eligible for run-in mainly due to glycosylated hemoglobin (HbA1c) value at screening visit being out of the protocol defined range.

After 2 weeks screening period, 1479 participants underwent 4-week run-in period. 309 participants were run-in failures. A total of 1170 participants were randomized in 2:2:1 to insulin glargine/lixisenatide, insulin glargine and lixisenatide arms respectively in open-label treatment period.

Participant milestones

Participant milestones
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) FRC injected subcutaneously once daily (QD) for 30 weeks. Dose individually adjusted.	Insulin Glargine Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Study STARTED	469	467	234
Overall Study Treated	469	467	233
Overall Study COMPLETED	440	440	205
Overall Study NOT COMPLETED	29	27	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) FRC injected subcutaneously once daily (QD) for 30 weeks. Dose individually adjusted.	Insulin Glargine Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Overall Study Randomized but not treated	0	0	1
Overall Study Adverse Event	12	9	21
Overall Study Lack of Efficacy	1	0	3
Overall Study Poor compliance to protocol	8	9	4
Overall Study Other than specified	8	9	0

Baseline Characteristics

Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination Compared to Insulin Glargine Alone and Lixisenatide Alone on Top of Metformin in Patients With T2DM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=469 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=467 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=234 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).	Total n=1170 Participants Total of all reporting groups
Age, Continuous	58.2 years STANDARD_DEVIATION 9.5 • n=93 Participants	58.3 years STANDARD_DEVIATION 9.4 • n=4 Participants	58.7 years STANDARD_DEVIATION 8.7 • n=27 Participants	58.4 years STANDARD_DEVIATION 9.3 • n=483 Participants
Sex: Female, Male Female	247 Participants n=93 Participants	230 Participants n=4 Participants	101 Participants n=27 Participants	578 Participants n=483 Participants
Sex: Female, Male Male	222 Participants n=93 Participants	237 Participants n=4 Participants	133 Participants n=27 Participants	592 Participants n=483 Participants
Race Caucasian	417 Participants n=93 Participants	421 Participants n=4 Participants	216 Participants n=27 Participants	1054 Participants n=483 Participants
Race Black	33 Participants n=93 Participants	33 Participants n=4 Participants	12 Participants n=27 Participants	78 Participants n=483 Participants
Race Asian/Oriental	8 Participants n=93 Participants	7 Participants n=4 Participants	3 Participants n=27 Participants	18 Participants n=483 Participants
Race Other	11 Participants n=93 Participants	6 Participants n=4 Participants	3 Participants n=27 Participants	20 Participants n=483 Participants
Ethnicity Hispanic	85 Participants n=93 Participants	87 Participants n=4 Participants	51 Participants n=27 Participants	223 Participants n=483 Participants
Ethnicity Not Hispanic	384 Participants n=93 Participants	380 Participants n=4 Participants	183 Participants n=27 Participants	947 Participants n=483 Participants
Second Oral Anti-diabetic Drug (OAD) Use Yes	274 Participants n=93 Participants	270 Participants n=4 Participants	133 Participants n=27 Participants	677 Participants n=483 Participants
Second Oral Anti-diabetic Drug (OAD) Use No	195 Participants n=93 Participants	197 Participants n=4 Participants	101 Participants n=27 Participants	493 Participants n=483 Participants
Second OAD Use at Screening by Class Sulfonylurea	259 Participants n=93 Participants	249 Participants n=4 Participants	123 Participants n=27 Participants	631 Participants n=483 Participants
Second OAD Use at Screening by Class Glinide	3 Participants n=93 Participants	10 Participants n=4 Participants	5 Participants n=27 Participants	18 Participants n=483 Participants
Second OAD Use at Screening by Class Sodium-glucose co-transporter-2 inhibitor	2 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	4 Participants n=483 Participants
Second OAD Use at Screening by Class Dipeptidyl peptidase-4 inhibitor	12 Participants n=93 Participants	11 Participants n=4 Participants	5 Participants n=27 Participants	28 Participants n=483 Participants
Second OAD Use at Screening by Class None	193 Participants n=93 Participants	195 Participants n=4 Participants	101 Participants n=27 Participants	489 Participants n=483 Participants
Body Mass Index (BMI)	31.64 kg/m^2 STANDARD_DEVIATION 4.4 • n=93 Participants	31.66 kg/m^2 STANDARD_DEVIATION 4.51 • n=4 Participants	31.99 kg/m^2 STANDARD_DEVIATION 4.39 • n=27 Participants	31.72 kg/m^2 STANDARD_DEVIATION 4.44 • n=483 Participants
Duration of Diabetes	8.89 years STANDARD_DEVIATION 5.51 • n=93 Participants	8.66 years STANDARD_DEVIATION 5.59 • n=4 Participants	8.89 years STANDARD_DEVIATION 6.26 • n=27 Participants	8.80 years STANDARD_DEVIATION 5.69 • n=483 Participants
Daily Dose of Metformin	2246.1 mg STANDARD_DEVIATION 456.8 • n=93 Participants	2244.7 mg STANDARD_DEVIATION 444.7 • n=4 Participants	2267.3 mg STANDARD_DEVIATION 427.4 • n=27 Participants	2249.8 mg STANDARD_DEVIATION 445.9 • n=483 Participants
HbA1c	8.08 percentage of HbA1c STANDARD_DEVIATION 0.71 • n=93 Participants	8.08 percentage of HbA1c STANDARD_DEVIATION 0.69 • n=4 Participants	8.13 percentage of HbA1c STANDARD_DEVIATION 0.72 • n=27 Participants	8.09 percentage of HbA1c STANDARD_DEVIATION 0.70 • n=483 Participants
Fasting Plasma Glucose (FPG)	9.87 mmol/L STANDARD_DEVIATION 2.35 • n=93 Participants	9.75 mmol/L STANDARD_DEVIATION 2.32 • n=4 Participants	9.75 mmol/L STANDARD_DEVIATION 2.19 • n=27 Participants	9.80 mmol/L STANDARD_DEVIATION 2.31 • n=483 Participants

PRIMARY outcome

Timeframe: Baseline, Week 30

Population: Modified intent-to-treat (mITT) population: all randomized participants who had both baseline and at least one post-baseline efficacy assessment. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during study period.

Primary outcome was to test superiority of FRC versus Lixisenatide and non-inferiority versus Insulin glargine. Change in HbA1c was calculated by subtracting baseline value from Week 30 value.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=467 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=464 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Change in HbA1c From Baseline to Week 30	-1.63 percentage of hemoglobin Standard Error 0.038	-1.34 percentage of hemoglobin Standard Error 0.039	-0.85 percentage of hemoglobin Standard Error 0.052

SECONDARY outcome

Timeframe: Week 30

Population: mITT population.

Participants without Week 30 value for HbA1c were counted as non-responders.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=468 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=466 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30 HbA1c ≤6.5%	55.8 percentage of participants	39.5 percentage of participants	19.3 percentage of participants
Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30 HbA1c <7.0%	73.7 percentage of participants	59.4 percentage of participants	33 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 30

Population: mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline plasma glucose excursion assessment during study period.

Plasma glucose excursion = 2-hour postprandial plasma glucose (PPG) value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 30 value. Missing data was imputed using last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=428 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=425 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=192 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Change in Plasma Glucose Excursion From Baseline to Week 30	-2.31 mmol/L Standard Error 0.154	-0.18 mmol/L Standard Error 0.157	-3.23 mmol/L Standard Error 0.216

SECONDARY outcome

Timeframe: Baseline, Week 30

Population: mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline body weight assessment during study period.

Change in body weight was calculated by subtracting baseline value from Week 30 value.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=467 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=465 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Change in Body Weight From Baseline to Week 30	-0.29 kg Standard Error 0.182	1.11 kg Standard Error 0.183	-2.3 kg Standard Error 0.256

SECONDARY outcome

Timeframe: Baseline, Week 30

Population: mITT population. Here, number of participants analysed = participants with baseline and at least one post-baseline FPG assessment during study period.

Change in FPG was calculated by subtracting baseline value from Week 30 value.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=465 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=465 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=232 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 30	-3.46 mmol/L Standard Error 0.09	-3.27 mmol/L Standard Error 0.091	-1.5 mmol/L Standard Error 0.124

SECONDARY outcome

Timeframe: Baseline, Week 30

Population: mITT population. Here,number of participants analyzed = participants with baseline and at least one post baseline 7-point SMPG assessment during study period.

Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime two times in a week before baseline, before visit Week 12 and before visit Week 30 and the average value across the profiles performed in the week before a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 30 value. The analysis included all scheduled measurements obtained during the study. The missing data was handled by mixed effect model with repeated measures (MMRM) approach.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=421 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=411 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=204 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30	-3.35 mmol/L Standard Deviation 0.081	-2.66 mmol/L Standard Deviation 0.084	-1.95 mmol/L Standard Deviation 0.111

SECONDARY outcome

Timeframe: Week 30

Population: mITT population. Participants without any HbA1c and/or body weight value at Week 30 were counted as non-responders.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=468 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=466 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30	43.2 percentage of participants	25.1 percentage of participants	27.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 30

Population: mITT population. Participants without any HbA1c and/or body weight value at Week 30 were counted as non-responders.

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).

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=468 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=466 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 and No Documented Symptomatic Hypoglycemia (Plasma Glucose [PG] ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period	31.8 percentage of participants	18.9 percentage of participants	26.2 percentage of participants

SECONDARY outcome

Timeframe: Week 30

Population: mITT population. Here, number of participants analyzed = participants with insulin glargine dose assessment during study period. Data of this endpoint was planned to be analyzed for Insulin Glargine/Lixisenatide FRC and Insulin glargine arms only, not for lixisenatide arm.

The analysis included scheduled measurements obtained up to the date of last injection of the IMP, including those obtained after introduction of rescue therapy.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=467 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=463 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Average Daily Insulin Glargine Dose at Week 30	39.77 Units (U) Standard Error 0.699	40.46 Units (U) Standard Error 0.701	—

SECONDARY outcome

Timeframe: Baseline, Week 30

Population: mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline 2-hour PPG assessment during study period.

The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 30 value. Missing data was imputed using LOCF.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=430 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=430 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=196 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Change in 2-Hour Postprandial Plasma Glucose (PPG) From Baseline to Week 30	-5.68 mmol/L Standard Error 0.176	-3.31 mmol/L Standard Error 0.178	-4.58 mmol/L Standard Error 0.245

SECONDARY outcome

Timeframe: Baseline up to Week 30

Population: mITT population. Participants without Week 30 value for HbA1c were counted as non-responders.

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). The analysis included all HbA1c measurements at Week 30, including those obtained after the IMP discontinuation or the introduction of rescue medication.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=468 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=466 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Percentage of Participants Reaching HbA1c <7.0% at Week 30 With No Documented Symptomatic Hypoglycemia (PG ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period	53.6 percentage of participants	44.4 percentage of participants	30.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 30

Population: mITT population.

Routine fasting SMPG and central laboratory FPG (and HbA1c after Week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after Week 12) was performed. Threshold values - from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 30: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8%.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=468 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=466 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period	3.6 percentage of participants	3.4 percentage of participants	12.4 percentage of participants

SECONDARY outcome

Timeframe: First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)

Population: Analysis was performed on safety population defined as all randomized participants who received at least one dose of IMP regardless of the amount of treatment administered.

Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=469 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=467 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year	1.44 Events per subject-year	1.22 Events per subject-year	0.34 Events per subject-year

SECONDARY outcome

Timeframe: First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)

Population: Safety population.

Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of ≤ 70 mg/dL (3.9 mmol/L).

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=469 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=467 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Percentage of Participants With Documented Symptomatic Hypoglycemia	25.6 percentage of participants	23.6 percentage of participants	6.4 percentage of participants

SECONDARY outcome

Timeframe: First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)

Population: Safety population.

Severe symptomatic hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Plasma glucose measurements might not have been available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal was considered sufficient evidence that the event had been induced by a low plasma glucose concentration. Severe symptomatic hypoglycemia included all episodes in which neurological impairment was severe enough to prevent self-treatment, and which were thus thought to place participants at risk of injury to themselves or others.

Outcome measures

Outcome measures
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=469 Participants FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Insulin Glargine n=467 Participants Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted.	Lixisenatide n=233 Participants Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose).
Percentage of Participants With Severe Symptomatic Hypoglycemia	0 percentage of participants	0.2 percentage of participants	0 percentage of participants

Adverse Events

Insulin Glargine/Lixisenatide Fixed Ratio Combination

Serious events: 18 serious events

Other events: 138 other events

Deaths: 0 deaths

Insulin Glargine

Serious events: 19 serious events

Other events: 85 other events

Deaths: 0 deaths

Lixisenatide

Serious events: 9 serious events

Other events: 98 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Insulin Glargine/Lixisenatide Fixed Ratio Combination n=469 participants at risk FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted (median exposure: 211 days).	Insulin Glargine n=467 participants at risk Insulin glargine injected subcutaneously QD for 30 weeks. Dose individually adjusted (median exposure: 211 days).	Lixisenatide n=233 participants at risk Lixisenatide 10 mcg injected subcutaneously QD for 2 weeks, then 20 mcg QD (maintenance dose) median exposure: 211 days).
Infections and infestations Upper respiratory tract infection	7.0% 33/469 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	4.9% 23/467 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	5.2% 12/233 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.
Infections and infestations Nasopharyngitis	5.5% 26/469 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	5.4% 25/467 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	6.4% 15/233 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.
Nervous system disorders Headache	5.1% 24/469 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	3.2% 15/467 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	7.7% 18/233 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.
Gastrointestinal disorders Nausea	9.6% 45/469 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	3.6% 17/467 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	24.0% 56/233 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.
Gastrointestinal disorders Diarrhoea	9.0% 42/469 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	4.3% 20/467 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	9.0% 21/233 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.
Gastrointestinal disorders Vomiting	3.2% 15/469 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	1.5% 7/467 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.	6.4% 15/233 • All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 213) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent that is AEs that developed/worsened during 'on-treatment period' (time from first injection of open-label IMP up to 3 days after the last injection of IMP regardless of the introduction of rescue therapy). Analysis was done on safety population.

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER