Trial Outcomes & Findings for 24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years (NCT NCT00976937)

Last Updated: 2016-10-11

Results Overview

Percentage of patients who met both criteria (HbA1c \<7% at Week 24 and at least 5% weight loss from baseline at Week 24) is reported. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

319 participants

Primary outcome timeframe

Week 24

Results posted on

2016-10-11

Participant Flow

The study was conducted at 92 centers in 13 countries between August 31, 2009 and March 19, 2011.

A total of 620 patients were screened of which 301 (48.5%) were screen failures; main reason for screen failure was glycosylated hemoglobin (HbA1c) values being out of the defined protocol range (greater than or equal to 7% and less than or equal to 10%). A total of 319 patients were randomized.

Participant milestones

Participant milestones
Measure	Lixisenatide 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24.	Sitagliptin Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.
Overall Study STARTED	158	161
Overall Study Treated/Safety Population	158	161
Overall Study Modified Intent-to-Treat(mITT)Population	158	161
Overall Study COMPLETED	142	150
Overall Study NOT COMPLETED	16	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Lixisenatide 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 milligram (mg) capsule orally QD up to Week 24.	Sitagliptin Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.
Overall Study Adverse Event	4	5
Overall Study Lost to Follow-up	2	1
Overall Study Withdrawal by Subject	5	3
Overall Study Poor compliance to protocol	3	0
Overall Study Personal and Familial Reason	2	2

Baseline Characteristics

24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lixisenatide n=158 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo: lixisenatide 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24 along with placebo matching to sitagliptin 100 mg capsule orally QD up to Week 24.	Sitagliptin n=161 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo: sitagliptin 100 mg capsule orally QD up to Week 24 along with volume matching lixisenatide placebo 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to Week 24.	Total n=319 Participants Total of all reporting groups
Age, Continuous	42.7 years STANDARD_DEVIATION 5.2 • n=5 Participants	43.4 years STANDARD_DEVIATION 4.7 • n=7 Participants	43.1 years STANDARD_DEVIATION 4.9 • n=5 Participants
Sex: Female, Male Female	103 Participants n=5 Participants	88 Participants n=7 Participants	191 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	73 Participants n=7 Participants	128 Participants n=5 Participants
Race/Ethnicity, Customized Race: Caucasian/White	132 participants n=5 Participants	127 participants n=7 Participants	259 participants n=5 Participants
Race/Ethnicity, Customized Race: Black	8 participants n=5 Participants	11 participants n=7 Participants	19 participants n=5 Participants
Race/Ethnicity, Customized Race: Asian/Oriental	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Race: Other	17 participants n=5 Participants	22 participants n=7 Participants	39 participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: Hispanic	73 participants n=5 Participants	72 participants n=7 Participants	145 participants n=5 Participants
Race/Ethnicity, Customized Ethnicity: Non Hispanic	85 participants n=5 Participants	89 participants n=7 Participants	174 participants n=5 Participants
Glycosylated Hemoglobin (HbA1c)	8.16 percentage of hemoglobin STANDARD_DEVIATION 0.89 • n=5 Participants	8.09 percentage of hemoglobin STANDARD_DEVIATION 0.96 • n=7 Participants	8.12 percentage of hemoglobin STANDARD_DEVIATION 0.93 • n=5 Participants
Body Mass Index (BMI)	36.76 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 7.25 • n=5 Participants	36.76 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.34 • n=7 Participants	36.76 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.80 • n=5 Participants
Duration of Diabetes	4.40 years STANDARD_DEVIATION 3.86 • n=5 Participants	4.43 years STANDARD_DEVIATION 3.56 • n=7 Participants	4.42 years STANDARD_DEVIATION 3.70 • n=5 Participants
Body Weight	98.51 kilogram STANDARD_DEVIATION 23.48 • n=5 Participants	100.56 kilogram STANDARD_DEVIATION 23.77 • n=7 Participants	99.55 kilogram STANDARD_DEVIATION 23.61 • n=5 Participants
2-hour Postprandial Plasma Glucose (PPG)	13.77 millimole per liter (mmol/L) STANDARD_DEVIATION 3.78 • n=5 Participants	13.92 millimole per liter (mmol/L) STANDARD_DEVIATION 3.99 • n=7 Participants	13.84 millimole per liter (mmol/L) STANDARD_DEVIATION 3.88 • n=5 Participants
Fasting Plasma Glucose (FPG)	9.09 mmol/L STANDARD_DEVIATION 2.60 • n=5 Participants	8.96 mmol/L STANDARD_DEVIATION 2.59 • n=7 Participants	9.03 mmol/L STANDARD_DEVIATION 2.59 • n=5 Participants
Glucose Excursion	4.37 mmol/L STANDARD_DEVIATION 2.64 • n=5 Participants	4.48 mmol/L STANDARD_DEVIATION 2.59 • n=7 Participants	4.42 mmol/L STANDARD_DEVIATION 2.61 • n=5 Participants
Fasting Plasma Insulin (FPI)	108.56 picomole/liter (pmol/L) STANDARD_DEVIATION 82.03 • n=5 Participants	106.99 picomole/liter (pmol/L) STANDARD_DEVIATION 82.69 • n=7 Participants	107.76 picomole/liter (pmol/L) STANDARD_DEVIATION 82.23 • n=5 Participants
2-hour Postprandial Plasma Insulin	424.67 pmol/L STANDARD_DEVIATION 350.96 • n=5 Participants	420.45 pmol/L STANDARD_DEVIATION 302.17 • n=7 Participants	422.56 pmol/L STANDARD_DEVIATION 327.02 • n=5 Participants
Fasting C-Peptide	1.19 mmol/L STANDARD_DEVIATION 0.51 • n=5 Participants	1.20 mmol/L STANDARD_DEVIATION 0.52 • n=7 Participants	1.20 mmol/L STANDARD_DEVIATION 0.52 • n=5 Participants
2-hour Postprandial C-peptide	2.79 mmol/L STANDARD_DEVIATION 1.28 • n=5 Participants	2.92 mmol/L STANDARD_DEVIATION 1.35 • n=7 Participants	2.86 mmol/L STANDARD_DEVIATION 1.32 • n=5 Participants
Fasting Glucagon	59.12 nanogram/liter (ng/L) STANDARD_DEVIATION 15.81 • n=5 Participants	59.43 nanogram/liter (ng/L) STANDARD_DEVIATION 20.53 • n=7 Participants	59.28 nanogram/liter (ng/L) STANDARD_DEVIATION 18.32 • n=5 Participants
2-hour Postprandial Glucagon	66.36 ng/L STANDARD_DEVIATION 17.58 • n=5 Participants	67.72 ng/L STANDARD_DEVIATION 25.77 • n=7 Participants	67.04 ng/L STANDARD_DEVIATION 22.05 • n=5 Participants
Fasting Proinsulin	45.06 pmol/L STANDARD_DEVIATION 39.50 • n=5 Participants	44.62 pmol/L STANDARD_DEVIATION 36.42 • n=7 Participants	44.83 pmol/L STANDARD_DEVIATION 37.91 • n=5 Participants
2-hour Postprandial Proinsulin	105.50 pmol/L STANDARD_DEVIATION 75.38 • n=5 Participants	105.51 pmol/L STANDARD_DEVIATION 74.00 • n=7 Participants	105.51 pmol/L STANDARD_DEVIATION 74.57 • n=5 Participants
Fasting Proinsulin-to-Insulin Ratio	0.53 ratio STANDARD_DEVIATION 0.70 • n=5 Participants	0.59 ratio STANDARD_DEVIATION 0.73 • n=7 Participants	0.56 ratio STANDARD_DEVIATION 0.71 • n=5 Participants
2-hour Postprandial Proinsulin-to-Insulin Ratio	0.36 ratio STANDARD_DEVIATION 0.53 • n=5 Participants	0.32 ratio STANDARD_DEVIATION 0.24 • n=7 Participants	0.34 ratio STANDARD_DEVIATION 0.41 • n=5 Participants
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	6.30 milliunit * mmol /liter^2(mU * mmol/L^2) STANDARD_DEVIATION 5.08 • n=5 Participants	6.26 milliunit * mmol /liter^2(mU * mmol/L^2) STANDARD_DEVIATION 5.32 • n=7 Participants	6.28 milliunit * mmol /liter^2(mU * mmol/L^2) STANDARD_DEVIATION 5.20 • n=5 Participants
Homeostatic Model Assessment of Beta-cell Function (HOMA-beta)	62.01 percentage of normal beta cells function STANDARD_DEVIATION 59.78 • n=5 Participants	60.74 percentage of normal beta cells function STANDARD_DEVIATION 50.80 • n=7 Participants	61.36 percentage of normal beta cells function STANDARD_DEVIATION 55.29 • n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Population: mITT population included randomized patients who received at least 1 dose of study drug. Missing data was imputed using Last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Lixisenatide n=158 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=161 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24	12.0 percentage of participants	7.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed=patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.

Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=150 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=160 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Absolute Change From Baseline in HbA1c at Week 24	-0.66 percentage of hemoglobin Standard Error 0.094	-0.72 percentage of hemoglobin Standard Error 0.097

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=152 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=160 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Body Weight at Week 24	-2.51 kilogram Standard Error 0.294	-1.17 kilogram Standard Error 0.304

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline 2-hour PPG assessment during on-treatment period.

The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=129 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=139 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24	-3.35 mmol/L Standard Error 0.377	-1.44 mmol/L Standard Error 0.384

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline FPG assessment during on-treatment period.

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=153 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=161 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	-0.45 mmol/L Standard Error 0.193	-0.69 mmol/L Standard Error 0.198

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucose excursion assessment during on-treatment period.

Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=127 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=139 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Glucose Excursion at Week 24	-2.55 mmol/L Standard Error 0.272	-0.42 mmol/L Standard Error 0.275

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline plasma insulin assessment during on-treatment period and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.

Change was calculated for fasting plasma insulin and 2-hour post prandial plasma insulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=123 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=133 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24 FPI (n=119, 133)	-1.70 pmol/L Standard Error 6.789	-0.88 pmol/L Standard Error 7.020
Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24 2-hour PPI (n=123, 130)	-57.81 pmol/L Standard Error 22.788	-2.85 pmol/L Standard Error 23.309

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline C-peptide assessment during on-treatment period and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.

Change was calculated for fasting C-peptide and 2-hour postprandial C-peptide by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=125 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=139 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24 Fasting C-peptide (n= 123,139)	-0.02 nmol/L Standard Error 0.039	-0.02 nmol/L Standard Error 0.038
Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24 2-hour postprandial C-peptide (n=125, 139)	-0.15 nmol/L Standard Error 0.100	0.08 nmol/L Standard Error 0.101

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucagon assessment during on-treatment period and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.

Change was calculated for fasting glucagon and 2-hour postprandial glucagon by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=124 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=138 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24 Fasting Glucagon (n=124, 138)	1.89 ng/L Standard Error 1.667	3.52 ng/L Standard Error 1.661
Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24 2-hour postprandial Glucagon (n=124, 134)	-8.16 ng/L Standard Error 1.801	-4.38 ng/L Standard Error 1.824

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline proinsulin assessment during on-treatment period and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.

Change was calculated for fasting proinsulin and 2-hour postprandial proinsulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of the study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=125 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=140 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24 Fasting Proinsulin (n=125, 140)	-2.18 pmol/L Standard Error 3.172	-4.84 pmol/L Standard Error 3.154
Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24 2-hour postprandial Proinsulin (n=125, 139)	0.28 pmol/L Standard Error 6.502	-3.95 pmol/L Standard Error 6.477

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HOMA-IR assessment during on-treatment period.

HOMA-IR was derived from FPG and FPI as: (FPI \[micro units per milliliter\]\*FPG \[mmol/L\]) divided by 22.5. Change was calculated for HOMA-IR by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=118 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=133 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Insulin Resistance Assessed by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) at Week 24	-0.52 mU * mmol/L^2 Standard Error 0.366	-0.57 mU * mmol/L^2 Standard Error 0.378

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HOMA-beta assessment during on-treatment period.

HOMA-beta was derived from FPG and FPI as: (20\*FPI \[micro units/milliliter\]) divided by (FPG \[mmol/L\] minus 3.5). Change was calculated for HOMA-beta by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=118 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=133 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Beta Cell Function Assessed by Homeostasis Model Assessment-Beta (HOMA-beta) at Week 24	17.66 percentage of normal beta cells function Standard Error 9.652	17.79 percentage of normal beta cells function Standard Error 9.958

SECONDARY outcome

Timeframe: Week 24

Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.

The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=150 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=160 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24	24.0 percentage of participants	26.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: mITT population.

Routine fasting self-measured plasma glucose (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) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8.5%.

Outcome measures

Outcome measures
Measure	Lixisenatide n=158 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=161 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Percentage of Patients Requiring Rescue Therapy During 24-Week Period	9.5 percentage of participants	6.8 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24

Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Lixisenatide n=150 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=160 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24	40.7 percentage of participants	40.0 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 24

Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Lixisenatide n=152 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=160 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24	18.4 percentage of participants	11.9 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline proinsulin-to-insulin ratio assessment during on-treatment period and 'n' = patients with baseline and at least 1 post-baseline assessment for the specified category.

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.

Outcome measures

Outcome measures
Measure	Lixisenatide n=123 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=133 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Change From Baseline in Fasting Proinsulin-to-insulin Ratio and 2-hour Postprandial Proinsulin-to-insulin Ratio at Week 24 Fasting Proinsulin-to-insulin ratio (n=119, 133)	-0.08 ratio Standard Error 0.035	-0.17 ratio Standard Error 0.036
Change From Baseline in Fasting Proinsulin-to-insulin Ratio and 2-hour Postprandial Proinsulin-to-insulin Ratio at Week 24 2-hour PP Proinsulin-to-insulin ratio (n=123, 130)	-0.01 ratio Standard Error 0.025	-0.05 ratio Standard Error 0.026

OTHER_PRE_SPECIFIED outcome

Timeframe: First dose of study drug up to 3 days after the last dose administration

Population: Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.

Outcome measures

Outcome measures
Measure	Lixisenatide n=158 Participants 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=161 Participants Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia Symptomatic hypoglycemia	1 participants	3 participants
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia Severe symptomatic hypoglycemia	0 participants	0 participants

Adverse Events

Lixisenatide

Serious events: 3 serious events

Other events: 54 other events

Deaths: 0 deaths

Sitagliptin

Serious events: 3 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lixisenatide n=158 participants at risk 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=161 participants at risk Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Infections and infestations Abscess limb	0.00% 0/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.62% 1/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Immune system disorders Anaphylactic reaction	0.63% 1/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Vascular disorders Arteriovenous fistula	0.63% 1/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Hepatobiliary disorders Bile duct stone	0.00% 0/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.62% 1/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Renal and urinary disorders Nephrolithiasis	0.63% 1/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Renal and urinary disorders Renal failure	0.00% 0/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.62% 1/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Other adverse events

Other adverse events
Measure	Lixisenatide n=158 participants at risk 2-step initiation regimen of lixisenatide along with sitagliptin placebo.	Sitagliptin n=161 participants at risk Sitagliptin along with 2-step initiation regimen of volume matching lixisenatide placebo.
Infections and infestations Influenza	5.1% 8/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.1% 5/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Nasopharyngitis	6.3% 10/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.5% 12/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Dizziness	5.1% 8/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.1% 5/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Headache	12.7% 20/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	9.3% 15/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Diarrhoea	8.9% 14/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.5% 12/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Nausea	17.7% 28/158 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	6.8% 11/161 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment was 169.0 days in both lixisenatide and sitagliptin treatment arm. The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

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