A Trial Comparing the Efficacy and Safety of Insulin Degl... | NCT01952145

ID	Type	Description	Link
2012-004413-14	EudraCT Number
U1111-1135-1003	Other Identifier	WHO

Status Module

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Insulin degludec/liraglutide OD plus metformin	Experimental		Drug: insulin degludec/liraglutide
Insulin glargine OD plus metformin	Active Comparator		Drug: insulin glargine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
insulin degludec/liraglutide	Drug	Insulin degludec/liraglutide is injected subcutaneously s.c. (under the skin) once daily (OD). Dose individually adjusted. Subjects should continue their pre-trial treatment with metformin.

Outcomes Module

Measure	Description	Time Frame
Change From Baseline in HbA1c (Glycosylated Haemoglobin)	Change from baseline in HbA1c after 26 weeks of treatment	Week 0, week 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Body Weight	Change from baseline in body weight after 26 weeks of treatment	Week 0, week 26
Number of Treatment Emergent Confirmed Hypoglycaemic Episodes	Confirmed hypoglycaemic episodes were defined as either: Severe (i.e., an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions) or an episode biochemically confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia.

Eligibility Module

Eligibility Criteria

Inclusion Criteria: - Type 2 diabetes mellitus - HbA1c 7.0-10.0% [53-86 mmol/mol] (both inclusive) by central laboratory analysis - Current treatment with insulin glargine for at least 90 days prior to screening - Stable daily dose of insulin glargine between 20 units and 50 units (both inclusive) for at least 56 days prior to screening. Total daily dose should be within the range of 20-50 units, both inclusive, on the day of screening, but individual fluctuations of plus/minus 10 procent within the 56 days prior to screening are acceptable - Stable daily dose of metformin (above or equal to 1500 mg or max tolerated dose) for at least 90 days prior to screening - Body mass index (BMI) below or equal to 40 kg/m^2 Exclusion Criteria: - Any use of oral antidiabetic agents (OADs) (except for metformin) within 90 days prior to Visit 1 (screening) - Current use of any drug (except metformin and insulin glargine) or anticipated change inconcomitant medication, which in the investigator's opinion could interfere with the glucose metabolism (e.g. systemic corticosteroids) - Previous and/or current treatment with any insulin regimen other than basal insulin, e.g. prandial or pre-mixed insulin (short term treatment due to intercurrent illness includinggestational diabetes is allowed at the discretion of the investigator) - Previous and/or current treatment with glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exenatide, liraglutide) - Impaired liver function, defined as ALAT (alanine aminotransferase) above or equal to 2.5 times upper normal range (UNR) - Impaired renal function defined as serum-creatinine above or equal to 133 micromol/L (above or equal to 1.5 mg/dL) for males and above or equal to 125 micromol/L (1.4 mg/dL) for females, or as allowed according to local contraindications for metformin - Screening calcitonin above or equal to 50 ng/L - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2) - 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		Fresno	California	93720	United States
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26934259	Result	Lingvay I, Perez Manghi F, Garcia-Hernandez P, Norwood P, Lehmann L, Tarp-Johansen MJ, Buse JB; DUAL V Investigators. Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients With Uncontrolled Type 2 Diabetes: The DUAL V Randomized Clinical Trial. JAMA. 2016 Mar 1;315(9):898-907. doi: 10.1001/jama.2016.1252.
28294641

Label	URL
Clinical Trials at Novo Nordisk	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Insulin Degludec/Liraglutide (IDegLira)	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Insulin Degludec/Liraglutide (IDegLira)	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.
BG001	Insulin Glargine (IGlar)	Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00058.4± 9.8 BG00159.1± 9.3 BG00258.8± 9.5

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000135 BG001142 BG002

Glycated hemoglobin (HbA1c)

Mean

Standard Deviation

Percentage (%)

Title

Denominators

Categories

Title	Measurements
	BG0008.4± 0.9 BG0018.2± 0.9 BG002

Body weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00088.3± 17.5 BG00187.3± 15.8 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

Change From Baseline in HbA1c (Glycosylated Haemoglobin)

Change from baseline in HbA1c after 26 weeks of treatment

FAS was used for analysis of this endpoint. And FAS included all randomised subjects. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.

Posted

Mean

Standard Deviation

Percentage (%)

Week 0, week 26

ID	Title	Description
OG000	Insulin Degludec/Liraglutide (IDegLira)	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.
OG001	Insulin Glargine (IGlar)	Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.

Units	Counts
Participants	OG000278 OG001279

Title

Denominators

Categories

Title	Measurements
	OG000-1.81± 1.08 OG001-1.13± 0.98

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	This primary endpoint was analysed on the FAS using an ANCOVA model with treatment and region as fixed effects and baseline HbA1c value as covariate.	ANCOVA		< 0.001		Treatment contrast	-0.59			2-Sided	95	-0.74	-0.45					Non-Inferiority or Equivalence	Non-inferiority of IDegLira versus IGlar was considered as confirmed, if the 95% confidence interval (CI) for the mean treatment difference was entirely below 0.30%.

Secondary

Change From Baseline in Body Weight

Change from baseline in body weight after 26 weeks of treatment

FAS which included all randomised subjects was used for analysis of this endpoint. Missing values (including intermittent missing values) were imputed using LOCF method.

Posted

Mean

Standard Deviation

Week 0, week 26

ID	Title	Description
OG000	Insulin Degludec/Liraglutide (IDegLira)	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.
OG001	Insulin Glargine (IGlar)	Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.

Secondary

Number of Treatment Emergent Confirmed Hypoglycaemic Episodes

Confirmed hypoglycaemic episodes were defined as either: Severe (i.e., an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions) or an episode biochemically confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia.

The safety analysis set was used for analysis of this endpoint and this set included all subjects receiving at least one dose of trial product. Subjects contributed to the evaluation "as treated". Confirmed hypoglycaemic episodes were reported by 79 subjects in IdegLira arm and by 137 subjects in IGlar arm.

Posted

Number

Number of episodes

During 26 weeks of treatment

ID	Title	Description
OG000	Insulin Degludec/Liraglutide (IDegLira)	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Insulin Degludec/Liraglutide (IDegLira)	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.			5	278	52	278
EG001	Insulin Glargine (IGlar)	Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.			9	279	22	279

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected278 at risk EG0011 events1 affected279 at risk
Appendicitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected278 at risk EG0011 events1 affected279 at risk
Arrhythmia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected278 at risk EG0011 events1 affected279 at risk
Auricular perichondritis	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 events0 affected278 at risk EG0011 events1 affected279 at risk
Biliary colic	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected278 at risk EG0011 events1 affected279 at risk
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 events0 affected278 at risk EG0011 events1 affected279 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 events0 affected278 at risk EG0011 events1 affected279 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 events1 affected278 at risk EG0010 events0 affected279 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected278 at risk EG0011 events1 affected279 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 events0 affected278 at risk EG0011 events1 affected279 at risk
Postmenopausal haemorrhage	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 events1 affected278 at risk EG0010 events0 affected279 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 events1 affected278 at risk EG0010 events0 affected279 at risk
Rectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 events1 affected278 at risk EG0010 events0 affected279 at risk
Vertebrobasilar insufficiency	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 events1 affected278 at risk EG0010 events0 affected279 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00023 events20 affected278 at risk EG00110 events7 affected279 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00012 events11 affected278 at risk EG00128 events14 affected279 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00034 events26 affected278 at risk EG0013 events3 affected279 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00022 events14 affected278 at risk EG0015 events5 affected279 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
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