Dual Action of Liraglutide and Insulin Degludec in Type 2... | NCT01336023

NCT01336023

ID	Type	Description	Link
U1111-1119-1174	Other Identifier	WHO
2010-021560-15	EudraCT Number

Status Module

Label	Type	Intervention Names
IDeg	Experimental	Drug: insulin degludec
IDegLira	Experimental	Drug: insulin degludec/liraglutide
Lira	Experimental	Drug: liraglutide

Name	Type	Description	Arm Group Labels	Other Names
insulin degludec/liraglutide	Drug	Insulin degludec/liraglutide treatment will be initiated and titrated (individually adjusted) twice weekly according to the mean self measured plasma glucose (SMPG) (fasting). Insulin degludec/liraglutide is injected subcutaneously (under the skin) once daily.

Outcomes Module

Measure	Description	Time Frame
Mean Change From Baseline in HbA1c (Glycosylated Haemoglobin) at Week 26.	Values of mean change in HbA1c.	Week 0, week 26

Secondary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in Body Weight at Week 26	Values of mean change in body weight.	Week 0, Week 26
Number of Hypoglycaemic Episodes	Reported hypoglycemaic episodes are number of hypoglycemic events per 100 patient years of exposure.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects with type 2 diabetes
HbA1c 7.0-10.0 % (both inclusive) with the aim of a median HbA1c of 8.3%. Accordingly, when approximately 50% of the randomised subjects have a HbA1c above 8.3%, the remaining subjects randomised must have a HbA1c of below or equal to 8.3%, or when approximately 50% of the randomised subjects have a HbA1c of below or equal to 8.3%, the remaining subjects randomised must have a HbA1c above 8.3%
Male or female, age 18 years or above (Taiwan: 20 years or above for a site 653 in Taiwan: Taichung Veterans General Hospital)
Subjects on stable dose of 1-2 OADs (metformin [at least 1500 mg or max tolerated dose] or metformin [at least 1500 mg or max tolerated dose] + pioglitazone [at least 30 mg]) for at least 90 days prior to screening
Body Mass Index (BMI) maximum 40 kg/m^2

Exclusion Criteria:

Treatment with insulin (except for short-term treatment due to intercurrent illness at the discretion of the Investigator)
Treatment with GLP-1 (glucagon-like peptide-1) receptor agonists (eg exenatide, liraglutide), sulphonylurea or dipeptidyl peptidase 4 (DPP-4) inhibitors within 90 days prior to trial
Impaired liver function, defined as alanine aminotransferese (ALAT) at least 2.5 times Upper Normal Range (UNR) (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive)
Impaired renal function defined as serum-creatinine at least 133 mcmol/l (at least 1.5 mg/dl) for males and at least 125 mcmol/l (at least 1.4) for females, or as allowed according to local contraindications for metformin (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive)
Screening calcitonin at least 50 ng/L
Subjects with personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2)
Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the last 12 months and planned coronary, carotid or peripheral artery revascularisation procedures
Severe uncontrolled treated or untreated hypertension (systolic blood pressure at least 180 mm Hg or diastolic blood pressure at least 100 mm Hg)
Acute treatment required proliferative retinopathy or maculopathy (macular oedema)
History of chronic pancreatitis or idiopathic acute pancreatitis

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		Birmingham	Alabama	35216	United States
Novo Nordisk Investigational Site

PubMed Identifier	Type	Citation	Retractions
28332144	Background	Khunti K, Mohan V, Jain SM, Boesgaard TW, Begtrup K, Sethi B. Efficacy and Safety of IDegLira in Participants with Type 2 Diabetes in India Uncontrolled on Oral Antidiabetic Drugs and Basal Insulin: Data from the DUAL Clinical Trial Program. Diabetes Ther. 2017 Jun;8(3):673-682. doi: 10.1007/s13300-017-0252-9. Epub 2017 Mar 22.
26443290

Label	URL
Clinical Trials at Novo Nordisk	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	IDeg	Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	IDeg	Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
BG001	IDegLira	Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
BG002	Liraglutide	Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
BG003	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

The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 413, 833 and 413, respectively.

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG000413 ParticipantsBG001833 ParticipantsBG002413 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000413 ParticipantsBG001833 ParticipantsBG002

Body Weight

Mean

Standard Deviation

Title	Denominators	Categories
	ParticipantsBG000413 ParticipantsBG001833 ParticipantsBG002

Normalised Incremental Area under curve (AUC)

The area under the glucose concentration (AUC) curve during 0-4 hours after the start of a standardised meal. The incremental AUC was calculated using the trapezoidal method and the resulting area was divided length of the observation period to yield the (normalised) prandial increment in mmol/L. The data was derived from the subjects who underwent a standard meal test conducted at selected sites.

The number of subjects analysed in the IDeg, IDegLira and Liraglutide arms 63, 128 and 61, respectively.

Mean

Standard Deviation

mmol/L

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG001

Glycosylated haemoglobin (HbA1c)

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title	Denominators	Categories
	ParticipantsBG000413 ParticipantsBG001833 ParticipantsBG002

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

Mean Change From Baseline in HbA1c (Glycosylated Haemoglobin) at Week 26.

Values of mean change in HbA1c.

The FAS included all randomised subjects and missing data was imputed using LOCF. Three subjects did not have their case book signed off due to discontinuation of an investigator's participation in the trial; hence 1 subject from each arm was excluded from the FAS.

Posted

Mean

Standard Deviation

Percentage of glycosylated haemoglobin

Week 0, week 26

ID	Title	Description
OG000	IDeg	Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
OG001	IDegLira	Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
OG002	Liraglutide	Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.

Units	Counts
Participants	OG000413 OG001833 OG002414

Title

Denominators

Categories

Title	Measurements
	OG000-1.44± 1.03 OG001-1.91± 1.07 OG002-1.28± 1.13

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		ANCOVA				Treatment Contrast	-0.47			2-Sided	95	-0.58	-0.36			IDegLira minus IDeg		Non-Inferiority	Non-inferiority of IDegLira vs. IDeg was confirmed when 95% confidence interval for the treatment differences for change in HbA1c lies entirely below 0.3%. IDegLira minus IDeg
OG001

Secondary

Mean Change From Baseline in Body Weight at Week 26

Values of mean change in body weight.

Posted

Mean

Standard Deviation

Week 0, Week 26

ID	Title	Description
OG000	IDeg	Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
OG001	IDegLira	Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.

Secondary

Number of Hypoglycaemic Episodes

Reported hypoglycemaic episodes are number of hypoglycemic events per 100 patient years of exposure.

The Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparators. The missing data was imputed using LOCF. The number of subjects analysed in SAS for each arm are 412, 825 and 412, respectively.

Posted

Number

Events per 100 patient years of exposure

Weeks 0-26

ID	Title	Description
OG000	IDeg	Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
OG001	IDegLira	Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.

Secondary

Change From Baseline in Incremental Area Under the Curve 0-4h (iAUC0-4h) Derived From the Glucose Concentration Profile During Meal Test

Values of mean change in normalised iAUC0-4h values based on LOCF data derived from the glucose concentration profiles during a meal test. The meal test was performed at selected sites at baseline and after 26 weeks of treatment in the main trial period. The incremental AUC was calculated using the trapezoidal method and the resulting area was divided length of the observation period to yield the (normalised) prandial increment in mmol/L using the available valid glucose observations and the associated actual elapsed time point.

The number of subjects analysed were equal to study population in which the meal test was perfomed at selected sites. Missing data was imputed using LOCF.

Posted

Mean

Standard Deviation

mmol/L

Week 0, Week 26

ID	Title	Description
OG000	IDeg	Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
OG001	IDegLira	Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.

Secondary

Mean Actual Daily Insulin Dose

Mean of the actual doses recorded at visit 28 (Week 26).

The FAS included all randomised subjects. Missing data was imputed using LOCF. For 22 subjects, the dose values were missing hence did not contribute to the analysis. The comparison was made between the insulin products IDeg and IDeglira.

Posted

Mean

Standard Deviation

units

Week 26

ID	Title	Description
OG000	IDeg	Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.
OG001	IDegLira	Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	IDeg	Insulin degludec (IDeg: 100 U/mL) was injected once daily (OD) subcutaneously (s.c.) for 26 weeks (main trial) + 26 weeks (extension trial). IDeg treatment was initiated at a dose of 10 units and titrated twice weekly to the fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean fasting self-measured plasma glucose (SMPG) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	22	412	160	412
EG001	IDegLira	Insulin Degludec/Liraglutide (IDegLira: 100 U/3.6 mg per mL) was injected subcutaneously OD for 26 weeks(main trial) + 26 weeks (extension trial). IDegLira treatment was initiated at 10 dose steps (containing 10 units IDeg and 0.36 mg liraglutide) and titrated twice weekly to a fasting glycaemic target of 4.0-5.0 mmol/L (72-90 mg/dL) based on the mean SMPG (fasting) from 3 preceeding measurements. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	38	825	386	825
EG002	Liraglutide	Liraglutide (6 mg/mL) was injected subcutaneously OD for 26 weeks (main trial). Liraglutide treatment was initiated at a dose of 0.6 mg/day, and subsequently increased by 0.6 mg in weekly dose escalation steps to reach maximum dose of 1.8 mg/day. Subjects continued with liraglutide 1.8 mg once daily in the 26 week extension period. Pre-trial metformin/metformin + pioglitazone treatment was continued throughout the trial.	24	412	241	412

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0012 events2 affected825 at risk EG0021 events1 affected412 at risk
Angina pectoris	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0012 events2 affected825 at risk EG0022 events2 affected412 at risk
Angina unstable	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment	EG0002 events2 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Atrial fibrillation	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0021 events1 affected412 at risk
Coronary artery dilatation	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Coronary artery disease	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Goitre	Endocrine disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Angle closure glaucoma	Eye disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Cataract	Eye disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Necrotising retinitis	Eye disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Vitreous haemorrhage	Eye disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Gastritis	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0022 events1 affected412 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0022 events2 affected412 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Death	General disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Pyrexia	General disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Biliary colic	Hepatobiliary disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0012 events2 affected825 at risk EG0020 events0 affected412 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA Version 15.0	Systematic Assessment	EG0002 events2 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Abscess	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Appendicitis perforated	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Bronchitis	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Diverticulitis	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Gastroenteritis	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Gastroenteritis viral	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Localised infection	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Septic shock	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Subcutaneous abscess	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Urinary tract infection	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0011 events1 affected825 at risk EG0021 events1 affected412 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0021 events1 affected412 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Wrong drug administered	Injury, poisoning and procedural complications	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Obesity	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0023 events3 affected412 at risk
Pseudarthrosis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Bladder cancer stage 0, with cancer in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Endometrial cancer stage III	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Inflammatory carcinoma of breast stage III	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Pancreatic carcinoma stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Plasmacytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Prostate cancer stage II	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Thyroid neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Complicated migraine	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Guillain-Barre syndrome	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Hypertensive encephalopathy	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Syncope	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Anxiety	Psychiatric disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Renal colic	Renal and urinary disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Renal failure	Renal and urinary disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Renal failure acute	Renal and urinary disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Renal impairment	Renal and urinary disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Dysfunctional uterine bleeding	Reproductive system and breast disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0003 events2 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Lung consolidation	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0010 events0 affected825 at risk EG0020 events0 affected412 at risk
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Coronary arterial stent insertion	Surgical and medical procedures	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Coronary artery bypass	Surgical and medical procedures	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0012 events2 affected825 at risk EG0020 events0 affected412 at risk
Coronary revascularisation	Surgical and medical procedures	MedDRA Version 15.0	Systematic Assessment	EG0001 events1 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk
Percutaneous coronary intervention	Surgical and medical procedures	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0010 events0 affected825 at risk EG0021 events1 affected412 at risk
Femoral arterial stenosis	Vascular disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 events0 affected412 at risk EG0011 events1 affected825 at risk EG0020 events0 affected412 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0004 events4 affected412 at risk EG00134 events26 affected825 at risk EG00223 events21 affected412 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00033 events28 affected412 at risk EG001128 events84 affected825 at risk EG00294 events67 affected412 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0005 events5 affected412 at risk EG00135 events28 affected825 at risk EG00228 events22 affected412 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00021 events16 affected412 at risk EG001102 events85 affected825 at risk EG002118 events92 affected412 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG00010 events10 affected412 at risk EG00162 events41 affected825 at risk EG00254 events37 affected412 at risk
Nasopharyngitis	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG00074 events52 affected412 at risk EG001162 events115 affected825 at risk EG00281 events55 affected412 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA Version 15.0	Systematic Assessment	EG00040 events34 affected412 at risk EG00179 events64 affected825 at risk EG00237 events33 affected412 at risk
Lipase increased	Investigations	MedDRA Version 15.0	Systematic Assessment	EG00020 events18 affected412 at risk EG00155 events48 affected825 at risk EG00240 events35 affected412 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 15.0	Systematic Assessment	EG0002 events2 affected412 at risk EG00123 events22 affected825 at risk EG00232 events30 affected412 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG00023 events15 affected412 at risk EG00136 events30 affected825 at risk EG00227 events22 affected412 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG00023 events20 affected412 at risk EG00145 events45 affected825 at risk EG00229 events23 affected412 at risk
Dizziness	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG00014 events10 affected412 at risk EG00130 events24 affected825 at risk EG00225 events22 affected412 at risk
Headache	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG000143 events45 affected412 at risk EG001207 events106 affected825 at risk EG002100 events60 affected412 at risk

ID	Term
D003920	Diabetes Mellitus
D003924	Diabetes Mellitus, Type 2

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

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

ID	Term
C000613158	IDegLira
C571886	insulin degludec
D000069450	Liraglutide