Trial Outcomes & Findings for Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure (NCT NCT01117350)

Last Updated: 2014-04-11

Results Overview

The value at the end of the comparative period was defined as the last available HbA1c value measured during the comparative period plus 14 days after the last dose of Investigational Product (i.e. last-observation-carried-forward \[LOCF\] value).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

978 participants

Primary outcome timeframe

week 12, week 24

Results posted on

2014-04-11

Participant Flow

The first patient was enrolled on July 23, 2010. The 24-week comparative period was completed on October 5, 2012. The extension period was initiated on March 24, 2011 and completed on March 6, 2013.

A total of 1456 patients were screened in 136 centers, in 17 countries (Austria, Brazil, Canada, Czech Republic, Finland, France, Greece, Ireland, Israel, Mexico, Netherlands, Russian Federation Slovakia, Spain, Sweden, Turkey, USA). Among them, 478 (32.8%) patients were not randomized (main reason was Glycosylated Haemoglobin A1c out of range).

Participant milestones

Participant milestones
Measure	Insulin Glargine Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days	Liraglutide (Comparative Period)/ Insulin Glargine (Extension) Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24 (comparative period) For patients included in the extension period: Insulin Glargine (dosing same as above)
Comparative Period STARTED	489	489
Comparative Period TREATED = Safety Population	484	481
Comparative Period mITT Population	474	470
Comparative Period COMPLETED	447	414
Comparative Period NOT COMPLETED	42	75
Extension Period STARTED	0	210
Extension Period TREATED = Safety Population (Extension)	0	160
Extension Period mITT Population (Extension)	0	154
Extension Period COMPLETED	0	147
Extension Period NOT COMPLETED	0	63

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Glargine Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days	Liraglutide (Comparative Period)/ Insulin Glargine (Extension) Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24 (comparative period) For patients included in the extension period: Insulin Glargine (dosing same as above)
Comparative Period Not Treated	5	8
Comparative Period Adverse Event	6	33
Comparative Period Lost to Follow-up	11	7
Comparative Period Withdrawal by Subject	9	13
Comparative Period Protocol Violation	8	12
Comparative Period Lack of Efficacy	1	0
Comparative Period Physician Decision	0	1
Comparative Period Move to another city/country	2	1
Extension Period Not included in extension, not treated	0	50
Extension Period Adverse Event	0	2
Extension Period Protocol Violation	0	2
Extension Period Lost to Follow-up	0	2
Extension Period Withdrawal by Subject	0	3
Extension Period Lack of Efficacy	0	2
Extension Period Inclusion criteria not respected	0	1
Extension Period Prohibited medication	0	1

Baseline Characteristics

Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Glargine n=474 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.	Liraglutide n=470 Participants Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Total n=944 Participants Total of all reporting groups
Age, Continuous	57.07 years STANDARD_DEVIATION 8.78 • n=5 Participants	57.44 years STANDARD_DEVIATION 8.85 • n=7 Participants	57.25 years STANDARD_DEVIATION 8.81 • n=5 Participants
Sex: Female, Male Female	224 Participants n=5 Participants	207 Participants n=7 Participants	431 Participants n=5 Participants
Sex: Female, Male Male	250 Participants n=5 Participants	263 Participants n=7 Participants	513 Participants n=5 Participants
Body Mass Index (BMI) at week -2	32.00 kg/m² STANDARD_DEVIATION 4.24 • n=5 Participants	31.75 kg/m² STANDARD_DEVIATION 4.12 • n=7 Participants	31.88 kg/m² STANDARD_DEVIATION 4.18 • n=5 Participants
Duration of Type 2 diabetes	8.54 years n=5 Participants	8.41 years n=7 Participants	8.49 years n=5 Participants
At least one diabetic late complication Yes	212 participants n=5 Participants	223 participants n=7 Participants	435 participants n=5 Participants
At least one diabetic late complication No	262 participants n=5 Participants	247 participants n=7 Participants	509 participants n=5 Participants
Glycosylated Hemoglobin A1c (HbA1c) at week -2	9.04 percent STANDARD_DEVIATION 1.10 • n=5 Participants	9.11 percent STANDARD_DEVIATION 1.09 • n=7 Participants	9.07 percent STANDARD_DEVIATION 1.09 • n=5 Participants

PRIMARY outcome

Timeframe: week 12, week 24

Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one HbA1c value on treatment during the comparative period.

Outcome measures

Outcome measures
Measure	Liraglutide n=458 Participants Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=467 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period	45.9 percentage of participants	48.4 percentage of participants

SECONDARY outcome

Timeframe: baseline (week -2), week 12, week 24

Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one HbA1c value on treatment during the comparative period.

Percentage of patients with: \* HbA1c value at end of the comparative period (LOCF) lower than HbA1c baseline value AND \* HbA1c value at end of the comparative period (LOCF) ≥7%

Outcome measures

Outcome measures
Measure	Liraglutide n=458 Participants Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=467 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period	46.3 percentage of participants	47.1 percentage of participants

SECONDARY outcome

Timeframe: baseline (week -2), week 12, week 24

Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one HbA1c value on treatment during the comparative period.

Percentage of patients with HbA1c value at end of the comparative period (LOCF) higher than HbA1c baseline value

Outcome measures

Outcome measures
Measure	Liraglutide n=458 Participants Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=467 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period	6.6 percentage of participants	4.1 percentage of participants

SECONDARY outcome

Timeframe: baseline (week -2), week 12, week 24

Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one HbA1c value on treatment during the comparative period.

Change in HbA1C from baseline to the last observation carried forward (LOCF) measured during the comparative period = LOCF value - baseline value

Outcome measures

Outcome measures
Measure	Liraglutide n=458 Participants Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=467 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period	-1.81 percent Standard Deviation 1.33	-1.92 percent Standard Deviation 1.22

SECONDARY outcome

Timeframe: week 24, week 36, week 48

Population: The population analyzed for this outcome measure consisted of the subset of mITT population (extension) who had HbA1c value both at beginning of the extension and at least one value on treatment during the extension period.

Change in HbA1C from beginning of the extension period (week 24) to the last observation carried forward (LOCF) measured during the extension period = LOCF value - week 24 value

Outcome measures

Outcome measures
Measure	Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=152 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period	—	-0.26 percent Standard Deviation 1.11

SECONDARY outcome

Timeframe: week 36, week 48

Population: The population analyzed for this outcome measure consisted of the mITT patients who had at least one HbA1c value on treatment during the extension period.

Value at the end of the extension period defined as last available HbA1c value measured during the extension period (i.e. last observation carried forward (LOCF) value)

Outcome measures

Outcome measures
Measure	Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=154 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period	—	22.7 percentage of participants

SECONDARY outcome

Timeframe: baseline (week 0), week 6, week 12, week 18, week 24

Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one SMFPG value on treatment during the comparative period.

SMFPG = mean value of Self-Monitored Fasting Plasma Glucose measurements over 3 consecutive days in the week before each visit Value at the end of the comparative period defined as last available value during the comparative period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - baseline value

Outcome measures

Outcome measures
Measure	Liraglutide n=452 Participants Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=468 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period	-37.23 mg/dL Standard Deviation 47.31	-65.25 mg/dL Standard Deviation 50.95

SECONDARY outcome

Timeframe: week 24, week 30, week 36, week 48

Population: The population analyzed for this outcome measure consisted of the subset of mITT (extension) patients who had SMFPG value both at beginning of the extension and at least one value on treatment during the extension period.

SMFPG = mean value of Self-Monitored Fasting Plasma Glucose measurements over 3 consecutive days in the week before each visit Value at the end of the extension period defined as last available value during the extension period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - week 24 value

Outcome measures

Outcome measures
Measure	Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=147 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of the Extension Period	—	-44.63 mg/dL Standard Deviation 45.47

SECONDARY outcome

Timeframe: baseline (week 0), week 12, week 24

Population: The population considered was the mITT population but due to missing values, different subsets of this mITT population were analyzed for each time point of the profile.

Self-monitored 7-point plasma glucose profiles (before and 2 hours after the start of breakfast, lunch and dinner, and at bedtime) recorded on 3 consecutive days in the week before each visit Value at the end of the comparative period defined as last available value during the comparative period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - baseline value

Outcome measures

Outcome measures
Measure	Liraglutide n=470 Participants Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=474 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period Before breakfast (N ig = 448 & N l = 409)	-38.64 mg/dL Standard Deviation 46.17	-65.92 mg/dL Standard Deviation 50.29
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period After breakfast (N ig = 440 & N l = 397)	-55.35 mg/dL Standard Deviation 61.56	-66.70 mg/dL Standard Deviation 63.29
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period Before lunch (N ig = 438 & N l = 404)	-39.13 mg/dL Standard Deviation 58.78	-50.16 mg/dL Standard Deviation 59.53
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period After lunch (N ig = 433 & N l = 406)	-41.82 mg/dL Standard Deviation 61.16	-43.00 mg/dL Standard Deviation 58.42
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period Before dinner (N ig = 434 & N l = 400)	-36.88 mg/dL Standard Deviation 58.49	-40.84 mg/dL Standard Deviation 58.88
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period After dinner (N ig = 426 & N l = 396)	-45.04 mg/dL Standard Deviation 60.42	-42.6 mg/dL Standard Deviation 61.74
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period At bedtime (N ig = 380 & N l = 351)	-44.06 mg/dL Standard Deviation 59.80	-43.11 mg/dL Standard Deviation 60.37

SECONDARY outcome

Timeframe: week 24, week 36, week 48

Population: The population considered was the mITT population (extension) but due to missing values, different subsets of this population were analyzed for each time point of the profile.

Self-monitored 7-point plasma glucose profiles (before and 2 hours after the start of breakfast, lunch and dinner, and at bedtime) recorded on 3 consecutive days in the week before each visit Value at the end of the extension period defined as last available value during the extension period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - week 24 value

Outcome measures

Outcome measures
Measure	Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=154 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period Before breakfast (N=143)	—	-46.13 mg/dL Standard Deviation 44.89
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period After breakfast (N=134)	—	-27.67 mg/dL Standard Deviation 52.37
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period Before lunch (N=131)	—	-20.32 mg/dL Standard Deviation 57.58
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period After lunch (N=134)	—	-11.50 mg/dL Standard Deviation 58.37
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period Before dinner (N=133)	—	-12.56 mg/dL Standard Deviation 54.57
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period After dinner (N=130)	—	-2.28 mg/dL Standard Deviation 54.55
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period At bedtime (N=127)	—	-14.94 mg/dL Standard Deviation 52.67

SECONDARY outcome

Timeframe: baseline (week 0), week 2, week 6, week 12, week 18, week 24

Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one weight value on treatment during the comparative period.

Change = Last weight value measured during the comparative period (LOCF value) - weight value at baseline

Outcome measures

Outcome measures
Measure	Liraglutide n=468 Participants Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=474 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Body Weight: Change From Baseline to the End of the Comparative Period	-2.99 kg Standard Deviation 3.64	1.98 kg Standard Deviation 3.95

SECONDARY outcome

Timeframe: week 24, week 30, week 36, week 48

Population: The population analyzed for this outcome measure consisted of the mITT population (extension).

Change = Last weight value measured during the extension period (LOCF value) - weight value at beginning of the Extension Period (Week 24)

Outcome measures

Outcome measures
Measure	Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=154 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Body Weight: Change From Beginning to End of the Extension Period	—	4.35 kg Standard Deviation 3.39

SECONDARY outcome

Timeframe: week 1, week 2, week 6, week 12, week 24

Population: The population considered was the mITT population but due to missing values, different subsets of this mITT population were analyzed at each week.

Outcome measures

Outcome measures
Measure	Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=474 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Daily Dose of Insulin Glargine Start of treatment (N=472)	—	13.39 Unit (U) Standard Deviation 4.87
Daily Dose of Insulin Glargine Week 1 (N=470)	—	17.74 Unit (U) Standard Deviation 6.52
Daily Dose of Insulin Glargine Week 2 (N=470)	—	22.06 Unit (U) Standard Deviation 8.40
Daily Dose of Insulin Glargine Week 6 (N=470)	—	34.67 Unit (U) Standard Deviation 17.03
Daily Dose of Insulin Glargine Week 12 (N=463)	—	44.40 Unit (U) Standard Deviation 26.63
Daily Dose of Insulin Glargine Week 18 (N=454)	—	48.65 Unit (U) Standard Deviation 31.03
Daily Dose of Insulin Glargine Week 24 (N=459)	—	51.67 Unit (U) Standard Deviation 34.05
Daily Dose of Insulin Glargine End comparative period (LOCF) (N=474)	—	51.24 Unit (U) Standard Deviation 33.93

SECONDARY outcome

Timeframe: week 1, week 2, week 6, week 12, week 24

Population: The population considered was the mITT population but due to missing values, different subsets of this mITT population were analyzed at each week.

Outcome measures

Outcome measures
Measure	Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=470 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Daily Dose of Liraglutide Start of treatment (N=470)	—	0.60 mg Standard Deviation 0.00
Daily Dose of Liraglutide Week 1 (N=463)	—	0.91 mg Standard Deviation 0.31
Daily Dose of Liraglutide Week 2 (N=458)	—	1.49 mg Standard Deviation 0.33
Daily Dose of Liraglutide Week 6 (N=444)	—	1.72 mg Standard Deviation 0.21
Daily Dose of Liraglutide Week 12 (N=426)	—	1.73 mg Standard Deviation 0.19
Daily Dose of Liraglutide Week 18 (N=415)	—	1.74 mg Standard Deviation 0.18
Daily Dose of Liraglutide Week 24 (N=431)	—	1.73 mg Standard Deviation 0.21
Daily Dose of Liraglutide End comparative period (LOCF) (N=470)	—	1.71 mg Standard Deviation 0.24

SECONDARY outcome

Timeframe: week 30, week 36, week 48

Population: The population considered was the mITT population (extension) but due to missing values, different subsets of this mITT population were analyzed at each week.

Outcome measures

Outcome measures
Measure	Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=154 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Daily Dose of Insulin Glargine Administered During the Extension Period Start of treatment (N=154)	—	15.77 Unit (U) Standard Deviation 4.53
Daily Dose of Insulin Glargine Administered During the Extension Period Week 30 (N=151)	—	37.49 Unit (U) Standard Deviation 15.70
Daily Dose of Insulin Glargine Administered During the Extension Period Week 36 (N=150)	—	46.21 Unit (U) Standard Deviation 23.06
Daily Dose of Insulin Glargine Administered During the Extension Period Week 48 (N=151)	—	50.68 Unit (U) Standard Deviation 27.33

SECONDARY outcome

Timeframe: all across the comparative period (from week 0 to week 24)

Population: The population analyzed was the safety population i.e. all randomized and treated patients.

Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia. Severe symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia, requiring the assistance of another person for active administration of carbohydrate, glucagon or other countermeasure because the patient could not treat him/herself due to acute neurological impairment directly resulting from the hypoglycemia (assistance by another person when the patient could have treated him/herself was not considered as requiring assistance)and one of the following criteria: * The event was associated with a measured PG level \< 36 mg/dL (2 mmol/L), * Or, in absence of PG value, the event was associated with neurological recovery attributable to the restoration of PG to normal, after oral carbohydrate, intravenous glucose or glucagon administration.

Outcome measures

Outcome measures
Measure	Liraglutide n=481 Participants Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=484 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period symptomatic hypoglycemia	85 participants	219 participants
Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period severe symptomatic hypoglycemia	2 participants	0 participants

SECONDARY outcome

Timeframe: all across the extension period (from week 24 to week 48)

Population: The population analyzed was the safety population (extension) i.e. all treated patients during the extension period.

Outcome measures

Outcome measures
Measure	Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24.	Insulin Glargine n=160 Participants Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days.
Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period symptomatic hypoglycemia	—	58 participants
Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period severe symptomatic hypoglycemia	—	0 participants

Adverse Events

Comparative Period: Insulin Glargine

Serious events: 11 serious events

Other events: 92 other events

Deaths: 0 deaths

Comparative Period: Liraglutide

Serious events: 15 serious events

Other events: 239 other events

Deaths: 0 deaths

Extension Period: Insulin Glargine

Serious events: 5 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Comparative Period: Insulin Glargine n=484 participants at risk Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days	Comparative Period: Liraglutide n=481 participants at risk Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24 (comparative period)	Extension Period: Insulin Glargine n=160 participants at risk Following a treatment with liraglutide during the comparative period, those patients have received insulin glargine during the extension period. Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days
Gastrointestinal disorders Constipation	1.2% 6/484 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	5.4% 26/481 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	0.00% 0/160 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.
Gastrointestinal disorders Diarrhoea	3.7% 18/484 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	12.9% 62/481 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	3.1% 5/160 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.
Gastrointestinal disorders Dyspepsia	0.83% 4/484 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	5.2% 25/481 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	0.62% 1/160 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.
Gastrointestinal disorders Nausea	2.7% 13/484 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	30.4% 146/481 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	1.2% 2/160 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.
Gastrointestinal disorders Vomiting	1.7% 8/484 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	9.6% 46/481 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	0.62% 1/160 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.
Infections and infestations Nasopharyngitis	7.9% 38/484 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	7.3% 35/481 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	7.5% 12/160 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.
Metabolism and nutrition disorders Decreased appetite	0.21% 1/484 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	9.4% 45/481 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	0.00% 0/160 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.
Nervous system disorders Headache	5.0% 24/484 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	6.0% 29/481 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.	1.2% 2/160 • Adverse events were collected throughout the study from the time the patient signed the informed consent until 7 days after the last dose of study treatment. The population analyzed was the safety population defined for each of the 2 periods (comparative and extension) as the patients treated with at least one dose of the study treatment during the considered period.

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 abstract/manuscript for comment at least 20/45 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