Efficacy Assessment of Insulin Glargine Versus Liraglutid... | NCT01117350

ID	Type	Description	Link
2010-018437-21	EudraCT Number
U1111-1116-9684	Other Identifier	UTN

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Insulin Glargine	Experimental	Insulin glargine administered once a day, in the morning or in the evening, at the most convenient time. The time of injection, once chosen was to remain unchanged during the whole duration of the study. The starting dose was 0.2 Unit per kilogram of body weight or 10 Units. Patients were empowered to adjust their insulin doses, under strict investigator's supervision. Insulin titration (by 2 or 4 Units) was done every 3 days according to the median value of Fasting Plasma Glucose (FPG) of the last 3 days. The goal was to achieve 70 < FPG ≤ 100 mg/dL (3.9 < FPG ≤ 5.5 mmol/L). Minor deviations from the titration scheme could be allowed, based on Investigator's judgment and patient's situation.	Drug: Insulin glargine Drug: Metformin
Liraglutide	Active Comparator	Liraglutide administered once a day, in the morning or in the evening, at the most convenient time. The time of injection , once chosen was to remain unchanged during the whole duration of the study. The dose was 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24. The dose might be decreased to 1.2 mg for safety reasons (e.g. gastro-intestinal tolerability), based on Investigator's judgment.	Drug: Liraglutide Drug: Metformin

Name	Type	Description	Arm Group Labels	Other Names
Insulin glargine	Drug	100 Units/mL solution for injection in a pre-filled SoloStar pen	Insulin Glargine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period	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).	week 12, week 24

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of 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%	baseline (week -2), week 12, week 24

Eligibility Module

Eligibility Criteria

Inclusion criteria (comparative period):

Patients With Type 2 Diabetes diagnosed for at least 1 year,
Treated with lifestyle interventions and metformin at the maximum tolerated dosage (with a minimum daily dosage of 1g), either alone or in combination with an oral insulin secretagogue (sulfonylurea, glinide or DiPeptidyl Peptidase IV inhibitor), for more than 3 months,
7.5% < HbA1c <= 12%,
Body Mass Index (BMI) between 25 and 40 kg/m2 inclusively,
Ability and willingness to perform PG (Plasma Glucose) self monitoring using the sponsor-provided glucose meter and to complete the patient diary,
Willingness and ability to comply with the study protocol,
Signed informed consent obtained prior to any study procedure.

Inclusion criteria (extension period):

Patients treated with liraglutide (at the maximal tolerated dosage), having a mean FPG ≥ 250 mg/dL at visit 10 (Week 12) or visit 11 (Week 18), or a HbA1c≥ 7% at visit 12 (Week 24)
Dosage of metformin compliant with the inclusion criteria of visit 1 (i.e. maximum tolerated dosage, with a minimum daily dosage of 1g), and maintained stable during the comparative period.

Exclusion criteria:

Previous treatment with Glucagon Like Peptide-1 analogues or insulin in the past year (except in case of temporary treatment for gestational diabetes, surgery, hospitalization...),
Treatment with thiazolidinediones or α-Glucosidases inhibitors within 3 months prior to study entry,
Diabetes other than Type 2 diabetes (e.g. secondary to pancreatic disorders, drug or chemical agents intake),
Pregnant women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method),
Lactating women,
Hospitalized patients (except hospitalization for routine diabetes check-up),
Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by a retina examination within 2 years prior to study entry,
Impaired renal function (creatinine clearance < 60 mL/mn),
Impaired hepatic function (Alanine Aminotransferase, Aspartate Aminotransferase 2.5 times the upper limit of normal range),
Personal or family history of medullary thyroid carcinoma,
Multiple endocrine neoplasia syndrome type 2,
Severe gastro-intestinal disease (including inflammatory bowel disease or diabetic gastroparesis),
Congestive heart failure,
History of acute pancreatitis,
Treatment with corticosteroids with potential systemic action for more than 10 days within 3 months prior to study entry,
Alcohol or drug abuse in the past 5 years,
History of sensitivity to the study drugs or to drugs with a similar chemical structure.
Night shift worker,
Presence of any condition (medical, psychological, social or geographical), current or anticipated that would compromise the patients safety or limit the patient successful participation in the study,
Participation in a clinical trial (drug or device) within 3 months prior to study entry,
Refusal or inability to give informed consent to participate in the study,
Patient is the Investigator or any sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

Additional exclusion criteria for the extension period:

Treatment with oral antidiabetic drugs other than metformin and patient's usual sulfonylurea if any, or with insulin during the comparative period (except in case of an emergency, for a period of time less than 7 days),
Treatment with corticosteroids with potential systemic action within the last 3 months of the comparative period.
History of sensitivity to insulin glargine.

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840023		Birmingham	Alabama	35294	United States
Investigational Site Number 840002

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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
FG001	Liraglutide (Comparative Period)/ Insulin Glargine (Extension)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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
	BG00057.07± 8.78 BG00157.44± 8.85 BG00257.25± 8.81

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000224 BG001207 BG002

Body Mass Index (BMI) at week -2

Mean

Standard Deviation

kg/m²

Title

Denominators

Categories

Title	Measurements
	BG00032.00± 4.24 BG00131.75± 4.12 BG002

Duration of Type 2 diabetes

Median

Inter-Quartile Range

years

Title

Denominators

Categories

Title	Measurements
	BG0008.54(5.20 to 12.38) BG0018.41(4.80 to 11.69) BG002

At least one diabetic late complication

Diabetic late complications: myocardial infarction, angina pectoris, coronary artery disease, heart failure, stroke, transient ischemic attack, peripheral vascular disease, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG000212 BG001

Glycosylated Hemoglobin A1c (HbA1c) at week -2

Mean

Standard Deviation

percent

Title

Denominators

Categories

Title	Measurements
	BG0009.04± 1.10 BG0019.11± 1.09 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period

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).

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.

Posted

Number

percentage of participants

week 12, week 24

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000467 OG001458

Title

Denominators

Categories

Title	Measurements
	OG00048.4 OG00145.9

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	Superiority testing H0: Rate measured with insulin glargine = rate measured with liraglutide H1: Rate measured with insulin glargine ≠ rate measured with liraglutide Sample size calculation (465 randomized patients per arm) was based on the assumption of an expected success rate of 46% with insulin glargine and 35% with liraglutide, an alpha risk of 5% (2-sided) and a power of 90%, taking into account an estimated non evaluability rate of 10%.	Chi-squared		0.439	If superiority not demonstrated, switching from superiority to non-inferiority considered. Conclusion of non-inferiority reached if lower limit of 2-sided 95% confidence interval of the difference (insulin glargine - liraglutide) > or = to - 3.5%	Mean Difference (Final Values)	2.54			2-Sided	95	-3.88	8.93

Secondary

Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of 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%

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.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period

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

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.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period

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

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.

Posted

Mean

Standard Deviation

percent

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of 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

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.

Posted

Mean

Standard Deviation

percent

week 24, week 36, week 48

ID	Title	Description
OG000	Insulin Glargine (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

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of 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)

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.

Posted

Number

percentage of participants

week 36, week 48

ID	Title	Description
OG000	Insulin Glargine (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

Units	Counts
Participants	OG000

Secondary

Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of 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

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.

Posted

Mean

Standard Deviation

mg/dL

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Secondary

Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of 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

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.

Posted

Mean

Standard Deviation

mg/dL

week 24, week 30, week 36, week 48

ID	Title	Description
OG000	Insulin Glargine (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

Units	Counts
Participants	OG000

Secondary

Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period

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

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.

Posted

Mean

Standard Deviation

mg/dL

baseline (week 0), week 12, week 24

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts

Secondary

Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period

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

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.

Posted

Mean

Standard Deviation

mg/dL

week 24, week 36, week 48

ID	Title	Description
OG000	Insulin Glargine (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

Units	Counts
Participants	OG000

Secondary

Body Weight: Change From Baseline to the End of the Comparative Period

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

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.

Posted

Mean

Standard Deviation

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000

Secondary

Body Weight: Change From Beginning to End of the Extension Period

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

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

Posted

Mean

Standard Deviation

week 24, week 30, week 36, week 48

ID	Title	Description
OG000	Insulin Glargine (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

Units	Counts
Participants	OG000

Secondary

Daily Dose of Insulin Glargine

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

Posted

Mean

Standard Deviation

Unit (U)

week 1, week 2, week 6, week 12, week 24

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000474

Secondary

Daily Dose of Liraglutide

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

Posted

Mean

Standard Deviation

week 1, week 2, week 6, week 12, week 24

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000470

Secondary

Daily Dose of Insulin Glargine Administered During the Extension Period

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

Posted

Mean

Standard Deviation

Unit (U)

week 30, week 36, week 48

ID	Title	Description
OG000	Insulin Glargine (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

Units	Counts
Participants	OG000154

Secondary

Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period

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.

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

Posted

Number

participants

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

ID	Title	Description
OG000	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.
OG001	Liraglutide

Secondary

Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period

Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia.

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.

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

Posted

Number

participants

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

ID	Title	Description
OG000	Insulin Glargine (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

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Comparative Period: 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	11	484	92	484
EG001	Comparative Period: 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 (comparative period)	15	481	239	481
EG002	Extension Period: Insulin Glargine	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	5	160	22	160

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrioventricular block second degree	Cardiac disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Cardiac arrest	Cardiac disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0010 affected481 at risk EG0021 affected160 at risk
Faecaloma	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Chest pain	General disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0010 affected481 at risk EG0021 affected160 at risk
Pyrexia	General disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Cellulitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Cystitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Diabetic gangrene	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Endocarditis bacterial	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Osteomyelitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Pneumonia	Infections and infestations	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0010 affected481 at risk EG0021 affected160 at risk
Urinary tract infection	Infections and infestations	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Blood glucose increased	Investigations	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0010 affected481 at risk EG0021 affected160 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Non-Hodgkin's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0012 affected481 at risk EG0020 affected160 at risk
Headache	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Ischaemic stroke	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Presyncope	Nervous system disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Suicidal behaviour	Psychiatric disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG0010 affected481 at risk EG0020 affected160 at risk
Oliguria	Renal and urinary disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0011 affected481 at risk EG0020 affected160 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA	Non-systematic Assessment	EG0000 affected484 at risk EG0010 affected481 at risk EG0021 affected160 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0006 affected484 at risk EG00126 affected481 at risk EG0020 affected160 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG00018 affected484 at risk EG00162 affected481 at risk EG0025 affected160 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0004 affected484 at risk EG00125 affected481 at risk EG0021 affected160 at risk
Nausea	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG00013 affected484 at risk EG001146 affected481 at risk EG0022 affected160 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Non-systematic Assessment	EG0008 affected484 at risk EG00146 affected481 at risk EG0021 affected160 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Non-systematic Assessment	EG00038 affected484 at risk EG00135 affected481 at risk EG00212 affected160 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA	Non-systematic Assessment	EG0001 affected484 at risk EG00145 affected481 at risk EG0020 affected160 at risk
Headache	Nervous system disorders	MedDRA	Non-systematic Assessment	EG00024 affected484 at risk EG00129 affected481 at risk EG0022 affected160 at risk

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

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
D052216	Glucagon-Like Peptide 1
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

ID	Term
D000069036	Insulin Glargine
D000069450	Liraglutide
D008687	Metformin