The Efficacy and Safety of Liraglutide as Adjunct Therapy... | NCT01836523

NCT01836523

ID	Type	Description	Link
2012-003580-21	EudraCT Number
U1111-1133-0590	Other Identifier	WHO

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	Intervention Names
Liraglutide 0.6 mg + insulin	Experimental	Drug: liraglutide
Liraglutide 1.2 mg + insulin	Experimental	Drug: liraglutide
Liraglutide 1.8 mg + insulin	Experimental	Drug: liraglutide
Liraglutide placebo 0.6 mg + insulin	Placebo Comparator	Drug: placebo
Liraglutide placebo 1.2 mg + insulin	Placebo Comparator	Drug: placebo
Liraglutide placebo 1.8 mg + insulin	Placebo Comparator	Drug: placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
liraglutide	Drug	Subjects randomised to 0.6 mg liraglutide treatment or liraglutide placebo as an add-on to their pre-trial insulin treatment will remain on this dose throughout the study (52 weeks). Administered subcutaneously (s.c., under the skin) once daily.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in HbA1c (Glycosylated Haemoglobin)	Change from baseline in HbA1c at week 52. Missing values were handled by using a mixed model for repeated measurements (MMRM).	Week 0, week 52
Change From Baseline in Body Weight	Change from baseline in body weight at week 52. Missing values were handled by using a MMRM.	Week 0, week 52
Change From Baseline in Total Daily Insulin Dose	Change from baseline in total daily insulin dose at week 52. Change from baseline was represented in terms of ratio to baseline for insulin dose i.e. Total daily insulin dose at week 52/total daily insulin dose at baseline. Missing values were handled by using a MMRM.	Week 0, week 52

Secondary Outcomes

Measure	Description	Time Frame
Number of Treatment-emergent Symptomatic Hypoglycaemic Episodes	This is a confirmatory secondary endpoint. Symptomatic hypoglycaemic episodes were defined as: 1) Severe according to the American Diabetes Association (ADA) classification: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. OR 2) Self-monitoring of plasma glucose value of <3.1 mmol/L, with symptoms consistent with hypoglycaemia. A treatment emergent episode is defined as an episode with onset date (or increase in severity) on or after first day of exposure to randomised treatment and up to last dose + 7 days.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Global Clinical Registry (GCR, 1452)	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novo Nordisk Investigational Site		Little Rock	Arkansas	72205	United States
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27506222	Result	Mathieu C, Zinman B, Hemmingsson JU, Woo V, Colman P, Christiansen E, Linder M, Bode B; ADJUNCT ONE Investigators. Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial. Diabetes Care. 2016 Oct;39(10):1702-10. doi: 10.2337/dc16-0691. Epub 2016 Aug 9.
39717993

Label	URL
Clinical Trials at Novo Nordisk	View source

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	Liraglutide 0.6 mg	Subjects received liraglutide 0.6 mg once daily (OD) subcutaneously for 52 weeks in addition to their pre-trial insulin treatment.
FG001	Liraglutide 1.2 mg

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

Liraglutide 0.6 mg + insulin

Subjects received liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.

Full analysis set (FAS) included all randomised subjects who received at least one dose and had any post-randomisation data. Five subjects, who started the study, were excluded because of no exposure to study drug and 4 subjects were excluded because of non-availability of post-baseline data.

Arm/Group Information

ID	Title	Description
BG000	Liraglutide 0.6 mg	Subjects received liraglutide 0.6 mg once daily (OD) subcutaneously for 52 weeks in addition to their pre-trial insulin treatment.
BG001	Liraglutide 1.2 mg	Subjects received liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.
BG002	Liraglutide 1.8 mg	Liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously for 2 weeks (weeks 2-4) followed by 1.8 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.
BG003	Placebo	Subjects received placebo (matched to liraglutide 0.6, 1.2 and 1.8 mg) OD subcutaneously as an add-on to their pre-trial insulin treatment. Placebo 0.1 mL (placebo matched to liraglutide 0.6 mg): Subjects received 0.1 mL liraglutide placebo for 52 weeks. Placebo 0.2 mL (placebo matched to liraglutide 1.2 mg): Subjects received 0.1 mL for 2 weeks followed by 0.2 mL up to week 52. Placebo 0.3 mL (placebo matched to liraglutide 1.8 mg): Subjects received 0.1 mL for 2 weeks followed by 0.2 mL for next 2 weeks and 0.3 mL up to week 52. All the 3 placebo doses were pooled for data analysis.
BG004	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
	BG00043.6± 12.78 BG00143.9± 13.06 BG00243.7± 13.33 BG003

Gender

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000186 BG001179 BG002

Glycosylated haemoglobin (HbA1c)

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.18± 0.738 BG0018.16± 0.779 BG002

Body weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00086.54± 17.338 BG00185.39± 17.210 BG002

Total daily actual insulin dose-continuous subcutaneous insulin infusion

Total insulin daily dose of subjects who were on continuous subcutaneous insulin infusion treatment. Number of subjects analysed=69 (liraglutide 0.6 mg), 99 (liraglutide 1.2 mg), 113 (liraglutide 1.8 mg), 95 (Placebo).

Geometric Mean

Full Range

units

Title

Denominators

Categories

Title	Measurements
	BG00052.97(13.8 to 137.1) BG001

Total daily actual insulin dose - Multiple daily injections

Total insulin daily dose of subjects who were on multiple daily insulin injection treatment. Number of subjects analysed=277 (liraglutide 0.6 mg), 242 (liraglutide 1.2 mg), 227 (liraglutide 1.8 mg), 250 (Placebo).

Geometric Mean

Full Range

units

Title

Denominators

Categories

Title	Measurements
	BG00059.54(22.9 to 181.6) BG001

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

Change From Baseline in HbA1c (Glycosylated Haemoglobin)

Change from baseline in HbA1c at week 52. Missing values were handled by using a mixed model for repeated measurements (MMRM).

Full analysis set. Number of subjects analysed=subjects with any post-baseline HbA1c data.

Posted

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Week 0, week 52

ID	Title	Description
OG000	Liraglutide 0.6 mg	Subjects received liraglutide 0.6 mg once daily (OD) subcutaneously for 52 weeks in addition to their pre-trial insulin treatment.
OG001	Liraglutide 1.2 mg	Subjects received liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.
OG002	Liraglutide 1.8 mg	Liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously for 2 weeks (weeks 2-4) followed by 1.8 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.
OG003	Placebo	Subjects received placebo (matched to liraglutide 0.6, 1.2 and 1.8 mg) OD subcutaneously as an add-on to their pre-trial insulin treatment. Placebo 0.1 mL (placebo matched to liraglutide 0.6 mg): Subjects received 0.1 mL liraglutide placebo for 52 weeks. Placebo 0.2 mL (placebo matched to liraglutide 1.2 mg): Subjects received 0.1 mL for 2 weeks followed by 0.2 mL up to week 52. Placebo 0.3 mL (placebo matched to liraglutide 1.8 mg): Subjects received 0.1 mL for 2 weeks followed by 0.2 mL for next 2 weeks and 0.3 mL up to week 52. All the 3 placebo doses were pooled for data analysis.

Units	Counts
Participants	OG000334 OG001312 OG002305 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.45± 0.741 OG001-0.50± 0.767 OG002-0.54± 0.729 OG003

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
OG002 OG003	Analysis was performed using MMRMs where all post-baseline measurements for the specific variable from planned visits up to week 52 and obtained no later than 1 day after withdrawal from treatment were entered as the dependent variable, and visit, treatment, country and the stratification variable (4 levels: HbA1c < 8.5% and ≥8.5%, each intersected by BMI≤27 kg/m2 and >27 kg/m2) were included as fixed factors and the corresponding baseline value as covariate.					Treatment difference	-0.20			2-Sided	95	-0.32	-0.07				Yes	Non-Inferiority or Equivalence

Primary

Change From Baseline in Body Weight

Change from baseline in body weight at week 52. Missing values were handled by using a MMRM.

Full analysis set. Number of subjects analysed=subjects with any post-baseline body weight data.

Posted

Mean

Standard Deviation

Week 0, week 52

ID	Title	Description
OG000	Liraglutide 0.6 mg	Subjects received liraglutide 0.6 mg once daily (OD) subcutaneously for 52 weeks in addition to their pre-trial insulin treatment.
OG001	Liraglutide 1.2 mg	Subjects received liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.
OG002	Liraglutide 1.8 mg	Liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously for 2 weeks (weeks 2-4) followed by 1.8 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.
OG003	Placebo	Subjects received placebo (matched to liraglutide 0.6, 1.2 and 1.8 mg) OD subcutaneously as an add-on to their pre-trial insulin treatment. Placebo 0.1 mL (placebo matched to liraglutide 0.6 mg): Subjects received 0.1 mL liraglutide placebo for 52 weeks. Placebo 0.2 mL (placebo matched to liraglutide 1.2 mg): Subjects received 0.1 mL for 2 weeks followed by 0.2 mL up to week 52. Placebo 0.3 mL (placebo matched to liraglutide 1.8 mg): Subjects received 0.1 mL for 2 weeks followed by 0.2 mL for next 2 weeks and 0.3 mL up to week 52. All the 3 placebo doses were pooled for data analysis.

Primary

Change From Baseline in Total Daily Insulin Dose

Change from baseline in total daily insulin dose at week 52. Change from baseline was represented in terms of ratio to baseline for insulin dose i.e. Total daily insulin dose at week 52/total daily insulin dose at baseline. Missing values were handled by using a MMRM.

Full analysis set. Number of subjects analysed=subjects with any post-baseline total insulin daily dose data.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

Week 0, week 52

ID	Title	Description
OG000	Liraglutide 0.6 mg	Subjects received liraglutide 0.6 mg once daily (OD) subcutaneously for 52 weeks in addition to their pre-trial insulin treatment.
OG001	Liraglutide 1.2 mg	Subjects received liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.
OG002	Liraglutide 1.8 mg	Liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously for 2 weeks (weeks 2-4) followed by 1.8 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.

Secondary

Number of Treatment-emergent Symptomatic Hypoglycaemic Episodes

This is a confirmatory secondary endpoint. Symptomatic hypoglycaemic episodes were defined as: 1) Severe according to the American Diabetes Association (ADA) classification: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. OR 2) Self-monitoring of plasma glucose value of <3.1 mmol/L, with symptoms consistent with hypoglycaemia. A treatment emergent episode is defined as an episode with onset date (or increase in severity) on or after first day of exposure to randomised treatment and up to last dose + 7 days.

The safety analysis set included all randomised subjects exposed to at least one dose of liraglutide or placebo.

Posted

Number

episodes

Weeks 0-52

ID	Title	Description
OG000	Liraglutide 0.6 mg	Subjects received liraglutide 0.6 mg once daily (OD) subcutaneously for 52 weeks in addition to their pre-trial insulin treatment.
OG001	Liraglutide 1.2 mg	Subjects received liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.
OG002	Liraglutide 1.8 mg

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Liraglutide 0.6 mg	Subjects received liraglutide 0.6 mg once daily (OD) subcutaneously for 52 weeks in addition to their pre-trial insulin treatment.	35	350	259	350
EG001	Liraglutide 1.2 mg	Subjects received liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.	36	348	263	348
EG002	Liraglutide 1.8 mg	Liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously for 2 weeks (weeks 2-4) followed by 1.8 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.	29	347	282	347
EG003	Placebo	Subjects received placebo (matched to liraglutide 0.6, 1.2 and 1.8 mg) OD subcutaneously as an add-on to their pre-trial insulin treatment. Placebo 0.1 mL (placebo matched to liraglutide 0.6 mg): Subjects received 0.1 mL liraglutide placebo for 52 weeks. Placebo 0.2 mL (placebo matched to liraglutide 1.2 mg): Subjects received 0.1 mL for 2 weeks followed by 0.2 mL up to week 52. Placebo 0.3 mL (placebo matched to liraglutide 1.8 mg): Subjects received 0.1 mL for 2 weeks followed by 0.2 mL for next 2 weeks and 0.3 mL up to week 52. All the 3 placebo doses were pooled for data analysis.	38	348	224	348

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG0031 events1 affected348 at risk
Angina pectoris	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Cardiac arrest	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Coronary artery disease	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Myocardial infarction	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Myocarditis	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Melkersson-Rosenthal syndrome	Congenital, familial and genetic disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Vertigo positional	Ear and labyrinth disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Glaucoma	Eye disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Macular oedema	Eye disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Retinopathy	Eye disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Nausea	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Rectal prolapse	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Vomiting	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Chest pain	General disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Cyst	General disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Malaise	General disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Anaphylactic reaction	Immune system disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Abscess	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Abscess limb	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Appendicitis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Arthritis bacterial	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Arthritis infective	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Cellulitis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Erysipelas	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Gastroenteritis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Herpes zoster	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Incision site infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Infectious mononucleosis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Otitis externa	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Pilonidal cyst	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Pneumonia	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Sepsis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Subcutaneous abscess	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Urinary tract infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0023 events3 affected347 at risk EG003
Wound infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Craniocerebral injury	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Ligament rupture	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Suture related complication	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Biopsy prostate	Investigations	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG0003 events3 affected350 at risk EG0011 events1 affected348 at risk EG0023 events3 affected347 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG0005 events3 affected350 at risk EG0014 events3 affected348 at risk EG0024 events3 affected347 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Hyperosmolar hyperglycaemic state	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG0004 events3 affected350 at risk EG0018 events7 affected348 at risk EG0025 events5 affected347 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Dupuytren's contracture	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0021 events1 affected347 at risk EG003
Joint effusion	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Haemangioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Haemangioma of bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Invasive lobular breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Cerebrospinal fluid leakage	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Hypoglycaemic seizure	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Hypoglycaemic unconsciousness	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0005 events5 affected350 at risk EG0013 events3 affected348 at risk EG0027 events6 affected347 at risk EG003
Migraine	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Alcoholism	Psychiatric disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Completed suicide	Psychiatric disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Depression	Psychiatric disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Depression suicidal	Psychiatric disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Panic attack	Psychiatric disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Suicide attempt	Psychiatric disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Bladder prolapse	Renal and urinary disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0011 events1 affected348 at risk EG0020 events0 affected347 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0021 events1 affected347 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Tonsillar inflammation	Respiratory, thoracic and mediastinal disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Diabetic foot	Skin and subcutaneous tissue disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Obesity surgery	Surgical and medical procedures	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Toe amputation	Surgical and medical procedures	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Hypertensive crisis	Vascular disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Peripheral vascular disorder	Vascular disorders	MedDra 18.0	Systematic Assessment	EG0001 events1 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003
Popliteal artery entrapment syndrome	Vascular disorders	MedDra 18.0	Systematic Assessment	EG0000 events0 affected350 at risk EG0010 events0 affected348 at risk EG0020 events0 affected347 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00032 events20 affected350 at risk EG00120 events16 affected348 at risk EG00241 events29 affected347 at risk EG0039 events8 affected348 at risk
Constipation	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00020 events17 affected350 at risk EG00130 events28 affected348 at risk EG00228 events26 affected347 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00052 events41 affected350 at risk EG00169 events50 affected348 at risk EG00292 events64 affected347 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00037 events26 affected350 at risk EG00141 events27 affected348 at risk EG00248 events38 affected347 at risk EG003
Nausea	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG000146 events112 affected350 at risk EG001196 events141 affected348 at risk EG002271 events172 affected347 at risk EG003
Vomiting	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00026 events24 affected350 at risk EG00158 events44 affected348 at risk EG002106 events64 affected347 at risk EG003
Fatigue	General disorders	MedDra 18.0	Systematic Assessment	EG00018 events17 affected350 at risk EG00124 events22 affected348 at risk EG00221 events18 affected347 at risk EG003
Gastroenteritis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00025 events21 affected350 at risk EG00117 events15 affected348 at risk EG00232 events29 affected347 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00014 events12 affected350 at risk EG0016 events6 affected348 at risk EG00224 events18 affected347 at risk EG003
Influenza	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00032 events29 affected350 at risk EG00126 events17 affected348 at risk EG00228 events25 affected347 at risk EG003
Nasopharyngitis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG000175 events105 affected350 at risk EG001124 events81 affected348 at risk EG002145 events83 affected347 at risk EG003
Sinusitis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00035 events24 affected350 at risk EG00122 events17 affected348 at risk EG00221 events16 affected347 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00037 events33 affected350 at risk EG00137 events23 affected348 at risk EG00259 events43 affected347 at risk EG003
Urinary tract infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00028 events18 affected350 at risk EG00121 events14 affected348 at risk EG00226 events20 affected347 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG00032 events31 affected350 at risk EG00145 events43 affected348 at risk EG00270 events64 affected347 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG00029 events17 affected350 at risk EG00126 events17 affected348 at risk EG00238 events22 affected347 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDra 18.0	Systematic Assessment	EG00032 events26 affected350 at risk EG00118 events13 affected348 at risk EG00237 events20 affected347 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG00017 events15 affected350 at risk EG00124 events22 affected348 at risk EG00219 events18 affected347 at risk EG003
Headache	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG00078 events56 affected350 at risk EG00185 events46 affected348 at risk EG002119 events49 affected347 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDra 18.0	Systematic Assessment	EG00014 events14 affected350 at risk EG0018 events7 affected348 at risk EG00212 events10 affected347 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDra 18.0	Systematic Assessment	EG00017 events15 affected350 at risk EG00124 events22 affected348 at risk EG00232 events28 affected347 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D003922	Diabetes Mellitus, Type 1

Ancestor Terms

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D000069450	Liraglutide

Ancestor Terms

ID	Term
D052216	Glucagon-Like Peptide 1
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

BG00250.46(8.7 to 150.2)

BG00349.18(3.9 to 176.1)

BG00450.65(3.9 to 176.1)

BG00262.52(16.4 to 271.3)

BG00362.42(20.3 to 230)

BG00460.94(16 to 282.5)

Non-inferiority was concluded if the upper bound of 95% confidence interval was <0.3.

Liraglutide 0.6 mg OD subcutaneously for 2 weeks followed by 1.2 mg OD subcutaneously for 2 weeks (weeks 2-4) followed by 1.8 mg OD subcutaneously up to week 52 in addition to their pre-trial insulin treatment.