Efficacy and Safety of Basal-bolus Therapy, Comparing Ste... | NCT01165684

NCT01165684

ID	Type	Description	Link
2010-018974-19	EudraCT Number
U1111-1116-0908	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

Label	Type	Description	Intervention Names
Step-wise	Experimental		Drug: insulin aspart Drug: insulin detemir
Basal-bolus	Active Comparator		Drug: insulin aspart Drug: insulin detemir

Interventions

Name	Type	Description	Arm Group Labels	Other Names
insulin aspart	Drug	Insulin aspart added stepwise according to the largest meal following an evaluation of HbA1c. Doses individually adjusted.	Step-wise

Outcomes Module

Measure	Description	Time Frame
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 32	Estimated mean change from baseline in HbA1c after 32 Weeks of treatment	Week 0, Week 32

Secondary Outcomes

Measure	Description	Time Frame
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 10	Estimated mean change from baseline in HbA1c after 10 Weeks of treatment	Week 0, Week 10
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 21

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Type 2 diabetes (diagnosed clinically) for at least 12 months
Basal insulin treatment (NPH once or twice daily, insulin glargine once daily or insulin detemir once daily) for at least 6 months
HbA1c: 7.0-9.0 % (both inclusive) by central laboratory analysis (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive)
BMI (Body Mass Index) less than 40.0 kg/m^2

Exclusion Criteria:

Previous use of pre-mix or bolus insulin (allowed is previous use of bolus insulin only in case of a hospitalisation or a severe condition requiring intermittent use of bolus insulin for less than 14 consecutive days, but not during the last 6 months prior to screening visit (Visit 1)
Use of GLP-1 (Glucagon-like peptide-1) receptor agonists or pramlintide within the last 6 months prior to prior to screening visit (Visit 1)
Anticipated change in concomitant medication known to interfere significantly with glucose metabolism (e.g. systemic corticosteroids, beta-blockers, MAO (Monoamine oxidase) inhibitors, etc.)
Cardiovascular disease, within the last 12 months prior to screening visit (Visit 1), defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty
Uncontrolled treated/untreated severe hypertension (systolic blood pressure sitting at least 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure at least 100 mmHg). For Argentina: systolic blood pressure sitting at least 150 mmHg and/or diastolic blood pressure at least 90 mmHg
Impaired liver function, defined as ALAT (Alanine aminotransferase) at least 2.5 times upper limit of normal (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive)
Impaired renal function defined as serum creatinine above 135 micromol/L (above 1.5 mg/dL) for males and above 110 micromol/L (above 1.2 mg/dL) for females; and, if required by the locally applicable metformin label, glomerular filtration rate below 60 ml/min, calculated by the Cockroft & Gault formula). One retest within a week is permitted with the result of the last sample being conclusive
Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode, during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months
Proliferative retinopathy or maculopathy requiring treatment according to the Investigator
Treatment with OADs (Oral anti-diabetic drug) contraindicated or unapproved for combination treatment with insulin (according to local OAD label)

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		Birmingham	Alabama	35216	United States
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24622667	Result	Rodbard HW, Visco VE, Andersen H, Hiort LC, Shu DH. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): a randomised, treat-to-target clinical trial. Lancet Diabetes Endocrinol. 2014 Jan;2(1):30-7. doi: 10.1016/S2213-8587(13)70090-1. Epub 2013 Sep 25.

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	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.

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

Estimated mean change from baseline in HbA1c after 21 Weeks of treatment

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
BG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
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
	BG00060.0± 9.1 BG00159.6± 9.5 BG00259.8± 9.3

Gender

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00097 BG001101 BG002

Body weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00088.9± 18.7 BG00186.1± 15.2 BG002

Body Mass Index (BMI)

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00031.5± 4.8 BG00130.7± 4.6 BG002

Glycosylated haemoglobin (HbA1c)

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0007.9± 0.6 BG0017.9± 0.6 BG002

Fasting plasma glucose (FPG)

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0007.0± 1.9 BG0016.9± 1.6 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 in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 32

Estimated mean change from baseline in HbA1c after 32 Weeks of treatment

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 32.

Posted

Mean

Standard Error

percentage of glycosylated haemoglobin

Week 0, Week 32

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts
Participants	OG000195 OG001188

Title

Denominators

Categories

Title	Measurements
	OG000-0.98± 0.06 OG001-1.12± 0.06

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		Regression, Linear		0.088		Estimated treatment difference, Mean	0.14				95	-0.02	0.30				Yes	Non-Inferiority or Equivalence	Non-inferiority was considered confirmed if the upper bound of the two-sided 95% CI was below or equal to 0.4% or equivalently if the p-value for the one-sided test of was less than or equal to 2.5%, where D is the mean treatment difference (step-wise regimen minus basal-bolus regimen).

Secondary

Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 10

Estimated mean change from baseline in HbA1c after 10 Weeks of treatment

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 376 subjects contributed to the statistical analysis at Week 10.

Posted

Mean

Standard Error

percentage of glycosylated haemoglobin

Week 0, Week 10

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts

Secondary

Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 21

Estimated mean change from baseline in HbA1c after 21 Weeks of treatment

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 21.

Posted

Mean

Standard Error

percentage of glycosylated haemoglobin

Week 0, Week 21

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts

Secondary

Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 10

Proportion of subjects reaching HbA1c below 7.0% at Week 10

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 376 subjects contributed to the statistical analysis at Week 10.

Posted

Number

percentage (%) of subjects

Week 10

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts

Secondary

Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 21

Proportion of subjects reaching HbA1c below 7.0% at Week 21

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 21.

Posted

Number

percentage (%) of subjects

Week 21

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts

Secondary

Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 32

Proportion of subjects reaching HbA1c below 7.0% at Week 32

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 32.

Posted

Number

percentage (%) of subjects

Week 32

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts

Secondary

Fasting Plasma Glucose (FPG) at Week 10

Mean FPG at Week 10

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 368 subjects contributed to data at Week 10.

Posted

Mean

Standard Deviation

mmol/L

Week 10

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts
Participants

Secondary

Fasting Plasma Glucose (FPG) at Week 21

Mean FPG at Week 21

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the data at Week 21.

Posted

Mean

Standard Deviation

mmol/L

Week 21

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts
Participants

Secondary

Fasting Plasma Glucose (FPG) at Week 32

Estimated Mean FPG at Week 32

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 32.

Posted

Mean

Standard Error

mmol/L

Week 32

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts
Participants

Secondary

Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 10

Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 10

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 326 subjects contributed to the data at Week 10.

Posted

Mean

Standard Deviation

mmol/L

Week 10

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts

Secondary

Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 21

Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 21

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 343 subjects contributed to the data at Week 21.

Posted

Mean

Standard Deviation

mmol/L

Week 21

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts

Secondary

Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 32

Estimated mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 32

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 352 subjects contributed to the statistical analysis at Week 32.

Posted

Mean

Standard Deviation

mmol/L

Week 32

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts

Secondary

Body Weight at Week 32

Estimated mean body weight after 32 Weeks of treatment

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 378 subjects contributed to the statistical analysis at Week 32.

Posted

Mean

Standard Error

Week 32

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts
Participants

Secondary

Body Mass Index (BMI) at Week 32

Estimated mean BMI after 32 Weeks of treatment

Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 378 subjects contributed to the statistical analysis at Week 32.

Posted

Mean

Standard Error

kg/m^2

Week 32

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

Units	Counts
Participants

Secondary

Hypoglycaemic Episodes (Rate of All Treatment Emergent Hypoglycaemia Episodes)

A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 1 day after the last day of randomised treatment.

Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator. 397 subjects contributed with data.

Posted

Number

Episodes /year of patient exposure

Week 0 to Week 32

ID	Title	Description
OG000	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
OG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.

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	Step-wise	In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.			18	198	40	198
EG001	Basal-bolus	In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.			15	199	47	199

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0011 events1 affected199 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Coronary artery disease	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Gastrointestinal fistula	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0011 events1 affected199 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Bacterial translocation	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0011 events1 affected199 at risk
Erysipelas	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0011 events1 affected199 at risk
Gastroenteritis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Injection site infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Wrong drug administered	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0011 events1 affected199 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0003 events2 affected198 at risk EG0016 events5 affected199 at risk
Gallbladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Metastatic gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Hypoglycaemic seizure	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0011 events1 affected199 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0013 events3 affected199 at risk
Acute stress disorder	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0011 events1 affected199 at risk
Lower respiratory tract inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0011 events1 affected199 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected198 at risk EG0010 events0 affected199 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected198 at risk EG0011 events1 affected199 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00010 events8 affected198 at risk EG00110 events10 affected199 at risk
Oedema peripheral	General disorders	MedDRA 15.0	Systematic Assessment	EG0005 events4 affected198 at risk EG00110 events10 affected199 at risk
Influenza	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00011 events10 affected198 at risk EG00114 events13 affected199 at risk
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00019 events16 affected198 at risk EG00118 events13 affected199 at risk
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG00015 events10 affected198 at risk EG00113 events11 affected199 at risk

A higher proportion of subjects did not complete the trial in the basal-bolus arm (52 subjects, 26.0%) than in the step-wise arm (28 subjects, 13.9%).

Certain Agreements

ID	Term
D003920	Diabetes Mellitus
D003924	Diabetes Mellitus, Type 2

ID	Term
D061267	Insulin Aspart
D000069057	Insulin Detemir

Ancestor Terms

ID	Term
D061266	Insulin, Short-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
D049528	Insulin, Long-Acting

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