Efficacy and Safety of the Insulin Glargine/Lixisenatide... | NCT02058160

NCT02058160

ID	Type	Description	Link
2013-003132-79	EudraCT Number
U1111-1148-4351	Other Identifier	UTN

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)	Experimental	FRC once daily (QD) for 30 weeks. Dose individually adjusted.	Drug: Insulin glargine/lixisenatide (HOE901/AVE0010) Drug: Metformin (Background Drug)
Insulin glargine	Active Comparator	Insulin glargine 100 U/mL QD for 30 weeks. Dose individually adjusted.	Drug: Insulin glargine (HOE901) Drug: Metformin (Background Drug)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Insulin glargine/lixisenatide (HOE901/AVE0010)	Drug	Insulin glargine/lixisenatide FRC was self-administered by subcutaneous (SC) injection within 1 hour before breakfast using one of 2 SoloStar® pen-injectors: Pen A (ratio of 2 Units (U) of insulin glargine U 100:1 mcg of lixisenatide) or Pen B (ratio of 3 U of insulin glargine U 100:1 mcg of lixisenatide). After run-in, the FRC was initiated at a dose of either 20 U/10 mcg with Pen A or 30 U/10 mcg with Pen B, depending on participant's dose of Insulin glargine on the day prior to randomization. Dose was adjusted weekly to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L). Pen A was used for administration of doses up to 40 U/20 mcg and Pen B for administration of doses from 30 U/10 mcg up to 60 U/20 mcg.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Glycated Hemoglobin (HbA1c) From Baseline to Week 30	Change in HbA1c was calculated by subtracting baseline value from Week 30 value.	Baseline, Week 30

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30		Week 30
Change in 2-hour Plasma Blood Glucose Excursion From Baseline to Week 30	Plasma glucose excursion = 2-hour postprandial glucose (PPG) minus plasma glucose value obtained 30 minutes prior to the start of the meal and before investigational medicinal product (IMP) administration, if IMP was injected before breakfast. Change in plasma glucose excursions was calculated by subtracting baseline value from Week 30 value.

Eligibility Module

Eligibility Criteria

Inclusion criteria :

Type 2 diabetes mellitus diagnosed at least 1 year before the screening visit.
Treatment with basal insulin for at least 6 months before the screening visit.
Stable basal insulin regimen (i.e. type of insulin and time/frequency of the injection) for at least 3 months before the screening visit.
Stable (plus/minus 20 percent) total daily basal insulin dose between 15 and 40 Units/day for at least 2 months prior to the screening visit.
For participants receiving basal insulin and 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s) must be stable during the 3 months before the screening visit. The OADs could be 1 to 2 out of:
- metformin (more than or equal to 1500 mg/day or maximal tolerated dose),
- a sulfonylurea,
- a glinide,
- a dipeptidyl-peptidase-4 inhibitor,
- a sodium glucose co-transporter 2 inhibitor,
Fasting Plasma Glucose (FPG) less than or equal to 180 mg/dL(10.0 mmol/L) at screening visit for participants receiving basal insulin in combination with 2 OADs or with 1 OAD other than metformin; FPG less than or equal to 200 mg/dL (11.1 mmol/L) at screening visit for participants on basal insulin only or basal insulin plus metformin at screening visit.
Signed written informed consent.

Exclusion criteria:

Age under legal age of adulthood at screening visit.
HbA1c at screening visit less than 7.5% or above 10%.
Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
Use of other oral or injectable glucose-lowering agents than stated in the inclusion criteria in a period of 3 months prior to screening.
Previous use of insulin other than basal insulin eg, prandial or pre-mixed insulin, in the year prior to screening. Note: Short term treatment (≤10 days) due to intercurrent illness is allowed.
History discontinuation of a previous treatment with Glucagon Like Peptide -1 Receptor Agonists for safety/tolerability or lack of efficacy.
Participant who had previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide FRC or had previously received lixisenatide.
Use of weight loss drugs within 3 months prior to screening visit.
Within the last 6 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period.
History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy, stomach/gastric surgery.
Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).
Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg) at screening visit.
At screening visit, Body Mass Index (BMI) less than or equal to 20 or above 40 kg/m^2.
At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN) laboratory range.
At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 3 ULN.
At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L).
Any contraindication to metformin use, according to local labeling, if the participant was taking metformin.
Participant who had a renal function impairment with creatinine clearance less than 30 mL/min (using the Cockcroft and Gault formula) or end-stage renal disease for participants, not treated with metformin.

Exclusion criteria for randomization:

HbA1c less than 7% or above 10% .
Mean fasting SMPG calculated from the self-measurements for 7 days the week before randomization visit was above 140 mg/dL (7.8 mmol/L).
Average insulin glargine daily dose less than 20 Units or above 50 Units (in the week before randomization visit).
Amylase and/or lipase more than 3 ULN .

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts/Locations Module

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840607		Birmingham	Alabama	35205	United States
Investigational Site Number 840570

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27650977	Result	Aroda VR, Rosenstock J, Wysham C, Unger J, Bellido D, Gonzalez-Galvez G, Takami A, Guo H, Niemoeller E, Souhami E, Bergenstal RM; LixiLan-L Trial Investigators. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: The LixiLan-L Randomized Trial. Diabetes Care. 2016 Nov;39(11):1972-1980. doi: 10.2337/dc16-1495. Epub 2016 Sep 20.
31848983

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)	FRC injected subcutaneously once daily (QD) for 30 weeks. Dose individually adjusted.
FG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
BG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-1.13± 0.057 OG001-0.62± 0.055

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis was performed using Mixed-effect model with repeated measures (MMRM) with treatment groups, randomization strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of metformin use at screening, visits, treatment-by-visit interaction and country as fixed effects and baseline HbA1c value-by-visit interaction as covariates. A hierarchical testing procedure was used to control type I error and handle multiple endpoint analyses.	Mixed Models Analysis		<0.0001	Threshold for significance at 0.05 level.	Least square (LS) mean difference	-0.52	Standard Error of the Mean	0.06	2-Sided	95	-0.633	-0.397			Insulin Glargine/Lixisenatide FRC vs Insulin Glargine

Secondary

Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30

mITT population. Participants with no value for HbA1c at Week 30 were counted as non-responders.

Posted

Number

percentage of participants

Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

Change in 2-hour Plasma Blood Glucose Excursion From Baseline to Week 30

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

mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline plasma glucose excursion assessment during study period. Missing data was imputed using last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants

Secondary

Change in Body Weight From Baseline to Week 30

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

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

Posted

Least Squares Mean

Standard Error

Baseline, Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30

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.

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

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts

Secondary

Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30

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

Posted

Number

percentage of participants

Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

Change in Daily Insulin Glargine Dose From Baseline to Week 30

mITT population. The analysis included scheduled measurements obtained up to the date of last injection of IMP. Here, number of participants analyzed= participants with insulin glargine dose assessment during study period.

Posted

Least Squares Mean

Standard Error

Units (U)

Baseline, Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

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

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).

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

Posted

Number

percentage of participants

Baseline up to Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

Change in FPG From Baseline to Week 30

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

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

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

Change in 2-hour PPG From Baseline to Week 30

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

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

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Reaching HbA1c <7.0% With No Documented Symptomatic Hypoglycemia (PG ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period

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).

mITT population. Participants with no value for HbA1c at Week 30 were counted as non-responders.

Posted

Number

percentage of participants

Baseline up to Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period

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) were 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%.

mITT population.

Posted

Number

percentage of participants

Baseline up to Week 30

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants

Secondary

Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year

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).

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.

Posted

Number

events per subject-year

First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Documented Symptomatic Hypoglycemia

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).

Analysis was performed on safety population.

Posted

Number

percentage of participants

First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Severe Symptomatic Hypoglycemia

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 had 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 for injury to themselves or others.

Analysis was performed on safety population.

Posted

Number

percentage of participants

First dose of study drug up to 1 day after the last dose administration (median treatment exposure 211 days [FRC], 210 days [Insulin glargine])

ID	Title	Description
OG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted.
OG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Insulin Glargine/Lixisenatide Fixed Ratio Combination	FRC injected subcutaneously QD for 30 weeks. Dose individually adjusted (median exposure: 211 days).			20	365	81	365
EG001	Insulin Glargine	Insulin glargine 100 U/mL injected subcutaneously QD for 30 weeks. Dose individually adjusted (median exposure: 210 days).			18	365	42	365

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0011 affected365 at risk
Osteomyelitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Wound infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Benign breast neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Benign gastric neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Squamous cell carcinoma of the tongue	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Gallbladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Kaposi's sarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected365 at risk EG0011 affected365 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected365 at risk EG0010 affected365 at risk
Hypoglycaemic seizure	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Glaucoma	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected365 at risk EG0010 affected365 at risk
Angina unstable	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected365 at risk EG0010 affected365 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Renal impairment	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Chest discomfort	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk
Non-cardiac chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0012 affected365 at risk
Scar	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected365 at risk EG0010 affected365 at risk
Meniscus injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected365 at risk EG0011 affected365 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00032 affected365 at risk EG00132 affected365 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00021 affected365 at risk EG00110 affected365 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00038 affected365 at risk EG0012 affected365 at risk

ID	Term
D003924	Diabetes Mellitus, Type 2

ID	Term
D000069036	Insulin Glargine
C479460	lixisenatide
D008687	Metformin

Ancestor Terms

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases