A Trial Comparing Efficacy and Safety of Insulin Degludec... | NCT01849289

ID	Type	Description	Link
U1111-1121-5325	Other Identifier	WHO

Status Module

Label	Type	Description	Intervention Names
Insulin Degludec	Experimental		Drug: Insulin Degludec
Insulin Glargine	Experimental		Drug: Insulin Glargine

Name	Type	Description	Arm Group Labels	Other Names
Insulin Degludec	Drug	Administered subcutaneously (under the skin), dose individually adjusted, once daily in combination with metformin at the unchanged, stable, pre-randomisation dose level and dosing frequency.

Outcomes Module

Measure	Description	Time Frame
Change From Baseline in HbA1c (%) (Analysed by Central Laboratory)	Change from baseline in HbA1c (%) after 26 weeks of treatment.	Week 0, week 26

Secondary Outcomes

Measure	Description	Time Frame
Number of Severe and Minor Treatment Emergent Hypoglycaemic Episodes	Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed PG value of less than 3.1 mmol/L (56 mg/dL).Minor hypoglycaemic episode is defined as an episode with symptoms consistent with hypoglycaemia with confirmation by full blood glucose < 2.8 mmol/L (50 mg/dL), or PG < 3.1 mmol/L (56 mg/dL) and which is handled by the subject himself/herself or any asymptomatic full blood glucose value < 2.8 mmol/L (50 mg/dL) or PG value < 3.1 mmol/L (56 mg/dL).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Type 2 diabetes mellitus (diagnosed clinically) for at least 6 months
Insulin naïve subjects (Allowed are: previous short term insulin treatment up to 14 days; treatment during hospitalisation or during gestational diabetes is allowed for periods longer than 14 days)
Current treatment: metformin monotherapy or metformin in any combination with an insulin secretagogue (sulfonylurea or glinide), dipeptidyl peptidase IV (DPP-IV) inhibitor, alfa-glucosidase-inhibitors (acarbose) with unchanged dosing for at least 3 months prior to randomisation (Visit 2) with the minimum doses stated: metformin: alone or in combination (including fixed combination) 1500 mg daily, or maximum tolerated dose (at least 1000 mg daily), insulin secretagogue (sulfonylurea or glinide): minimum half of the daily maximal dose according to local labelling, DPP-IV inhibitor: minimum 100 mg daily or according to local labelling, alfa-glucosidase-inhibitors (acarbose): minimum half of the daily maximal dose or maximum tolerated dose
HbA1c (glycosylated haemoglobin) 7.0-10.0% (both inclusive) by central laboratory analysis
BMI (Body Mass Index) below or equal to 40.0 kg/m^2

Exclusion Criteria:

Treatment with TZDs (thiazoledinedione), or GLP-1 (glucagon-like peptide 1) receptor agonists within the last 3 months prior to Visit 1 (screening)
Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as systemic corticosteroids, beta-blockers, MAO (monoamine oxidase) inhibitors
Cardiovascular disease within the last 6 months prior to Visit 1 (screening) defined as stroke; decompensated heart failure NYHA (New York Heart Association) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty
Any clinically significant disease or disorder, except for conditions associated with type 2 diabetes mellitus, which in the Investigator's opinion could interfere with the results of the trial
Previous participation in this trial. Participation is defined as randomised. Re-screening of screening failures is allowed only once within the limits of the recruitment period
Known or suspected hypersensitivity to trial product(s) or related products

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		Anaheim	California	92801	United States
Novo Nordisk Investigational Site

PubMed Identifier	Type	Citation	Retractions
27098525	Result	Pan C, Gross JL, Yang W, Lv X, Sun L, Hansen CT, Xu H, Wagner R. A Multinational, Randomized, Open-label, Treat-to-Target Trial Comparing Insulin Degludec and Insulin Glargine in Insulin-Naive Patients with Type 2 Diabetes Mellitus. Drugs R D. 2016 Jun;16(2):239-49. doi: 10.1007/s40268-016-0134-z.
28870034	Derived

Label	URL
Clinical Trials at Novo Nordisk	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	IDeg OD	Insulin degludec (IDeg) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	IDeg OD	Insulin degludec (IDeg) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).
BG001	IGlar OD	Insulin glargine (IGlar) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).
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
	BG00055.9± 9.7 BG00156.6± 9.2 BG00256.2± 9.6

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000256 BG001146 BG002

HbA1c

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.3± 0.9 BG0018.3± 0.8 BG002

Fasting Plasma Glucose (FPG)

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0009.4± 2.4 BG0019.4± 2.5 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 (%) (Analysed by Central Laboratory)

Change from baseline in HbA1c (%) after 26 weeks of treatment.

The FAS included all randomised subjects. Last Observation Carried Forward (LOCF) values were presented for this endpoint.

Posted

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Week 0, week 26

ID	Title	Description
OG000	IDeg OD	Insulin degludec (IDeg) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).
OG001	IGlar OD	Insulin glargine (IGlar) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).

Units	Counts
Participants	OG000555 OG001278

Title

Denominators

Categories

Title	Measurements
	OG000-1.3± 1.1 OG001-1.2± 1.0

Secondary

Number of Severe and Minor Treatment Emergent Hypoglycaemic Episodes

Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed PG value of less than 3.1 mmol/L (56 mg/dL).Minor hypoglycaemic episode is defined as an episode with symptoms consistent with hypoglycaemia with confirmation by full blood glucose < 2.8 mmol/L (50 mg/dL), or PG < 3.1 mmol/L (56 mg/dL) and which is handled by the subject himself/herself or any asymptomatic full blood glucose value < 2.8 mmol/L (50 mg/dL) or PG value < 3.1 mmol/L (56 mg/dL).

The Safety analysis set (SAS) included all subjects receiving at least one dose of the investigational product or its comparator.

Posted

Number

Episodes/100 years of patient exposure

On or after the first day of exposure to randomised trial drug (week 0) and no later than 7 days after last exposure to randomised trial drug (week 27)

ID	Title	Description
OG000	IDeg OD	Insulin degludec (IDeg) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).
OG001	IGlar OD	Insulin glargine (IGlar) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).

Secondary

Change From Baseline in FPG (Fasting Plasma Glucose) (Analysed by Central Laboratory)

Change from baseline in FPG after 26 weeks of treatment.

The FAS included all randomised subjects. LOCF values are presented for this endpoint. 7 subjects were not included in the analysis.

Posted

Mean

Standard Deviation

mmol/L

Week 0, week 26

ID	Title	Description
OG000	IDeg OD	Insulin degludec (IDeg) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).
OG001	IGlar OD	Insulin glargine (IGlar) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).

Secondary

Within-subject Variability as Measured by Coefficient of Variation (CV%) in Pre-breakfast SMPG (Self-measured Plasma Glucose)

Within subject Coefficient of variation(CV[%]) in pre-breakfast self measured plasma glucose for dose adjustment after 26 treatment weeks are displayed below.

The FAS included all randomised subjects. Missing data were imputed using LOCF. For 2 subjects in the IDeg OD arm it was not possible to estimate CV(%) due to missing data.

Posted

Mean

Standard Deviation

percentage

Week 26

ID	Title	Description
OG000	IDeg OD	Insulin degludec (IDeg) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).
OG001	IGlar OD	Insulin glargine (IGlar) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).

Secondary

Responder for HbA1c (Below 7.0%) at End of Trial Without Severe and Minor Hypoglycaemic Episodes

A responder for HbA1c without severe or confirmed hypoglycaemia is defined as a subject, who meets the HbA1c target at end of trial without treatment emergent severe or confirmed hypoglycaemia during the last 12 weeks of treatment or within 7 days from last treatment.

The FAS included all randomised subjects.

Posted

Number

participants

Week 26

ID	Title	Description
OG000	IDeg OD	Insulin degludec (IDeg) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).
OG001	IGlar OD	Insulin glargine (IGlar) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).

Secondary

Number of Treatment Emergent AEs (Adverse Events)

Treatment emergent events (after first trial product administration and no later than 7 days after last trial product administration)

The SAS included all subjects receiving at least one dose of investigational product.

Posted

Number

number of events

On or after the first day of exposure to randomised trial drug (week 0) and no later than seven days after last exposure to randomised trial drug (week 27)

ID	Title	Description
OG000	IDeg OD	Insulin degludec (IDeg) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).
OG001	IGlar OD	Insulin glargine (IGlar) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).

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	IDeg OD	Insulin degludec (IDeg) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).			16	553	100	553
EG001	IGlar OD	Insulin glargine (IGlar) 10U was injected subcutaneously (under the skin) once daily (OD) in the evening (start of main evening meal to bedtime) either in the thigh, upper arm (deltoid area) or abdomen along with metformin given orally for 26 weeks. At last treatment visit (Visit 28) subjects were instructed to switch basal insulin treatment to the intermediate acting insulin NPH until the follow-up visit (Visit 29).			10	278	58	278

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coronary artery stenosis	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected553 at risk EG0011 events1 affected278 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Palpitations	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected553 at risk EG0011 events1 affected278 at risk
Crohn's disease	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected553 at risk EG0011 events1 affected278 at risk
Gastric polyps	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Appendicitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0011 events1 affected278 at risk
Diverticulitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Gastroenteritis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Herpes zoster disseminated	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected553 at risk EG0011 events1 affected278 at risk
Pneumonia	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected553 at risk EG0011 events1 affected278 at risk
Pyelonephritis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0012 events2 affected278 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected553 at risk EG0011 events1 affected278 at risk
Haemangioma of liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Non-small cell lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 events0 affected553 at risk EG0011 events1 affected278 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0011 events1 affected278 at risk
Cerebral infarction	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0002 events2 affected553 at risk EG0011 events1 affected278 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0002 events2 affected553 at risk EG0010 events0 affected278 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected553 at risk EG0010 events0 affected278 at risk

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

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 16.1	Systematic Assessment		EG00049 events41 affected553 at risk EG00140 events27 affected278 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment		EG00077 events60 affected553 at risk EG00140 events32 affected278 at risk