Comparison of Biphasic Insulin Aspart 30 Individually Adj... | NCT01427920

NCT01427920

ID	Type	Description	Link
2010-024303-27	EudraCT Number
U1111-1118-4096	Other Identifier	WHO

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Subject-driven titration BIAsp 30 (BID) + metformin	Experimental	The subjects performed the titration of BIAsp 30 dose.	Drug: biphasic insulin aspart 30
Investigator-driven titration BIAsp 30 (BID) + metformin	Active Comparator	The investigator performed the titration of BIAsp 30 dose.	Drug: biphasic insulin aspart 30

Interventions

Name	Type	Description	Arm Group Labels	Other Names
biphasic insulin aspart 30	Drug	Administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in HbA1c (Glycosylated Haemoglobin) - FAS	Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in full analysis set (FAS).	Week 0, week 20
Change in HbA1c (Glycosylated Haemoglobin) - PP	Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in per protocol (PP) analysis set.	Week 0, week 20

Secondary Outcomes

Measure	Description	Time Frame
Change in Fasting Plasma Glucose (FPG) (Central Laboratory Values)	Estimated mean change from baseline in FPG after 20 Weeks of treatment	Week 0, week 20
Number of Treatment Emergent Hypoglycaemic Episodes

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosed with type 2 diabetes for a minimum of 12 months prior to Visit 1 (screening)
Currently treated with a basal insulin analogue for at least 3 months prior to Visit 1 (screening)
Stable treatment (no change in dose or regimen) with a total daily dose of at least 1500 mg metformin or maximum tolerated dose (minimum 1000 mg) ± additional OAD treatment. The metformin treatment must have been stable for at least 2 months prior to Visit 1 (screening)
HbA1c higher or equal to 7.0% and below or equal to 10.0% (one re-test within one week of screening visit was allowed. The last sample was to be conclusive)
Body Mass Index (BMI) below or equal to 40.0 kg/m^2
Able and willing to eat at least 2 main meals each day during the trial
Able and willing to adhere to the protocol including compliance with performance of self measured plasma glucose (SMPG), injection regimen and titrating themselves according to the protocol
Experience in performing self measured plasma glucose (SMPG)

Exclusion Criteria:

Treatment with any thiazolidinedione (TZD) and glucagon-like peptide-1 (GLP-1) receptor agonists or pramlintide within the last 3 months prior to Visit 1 (screening)
Impaired hepatic function defined as alanine aminotransferase (ALAT) above or equal to 2.5 times upper referenced limit (one re-test within one week of screening visit was allowed. The last sample was to be conclusive)
Impaired kidney function with serum creatinine above or equal to 133 micromol/L (1.5 mg/dL) for males and above or equal to 124 micromol/L (1.4 mg/dL) for females (one re-test within one week of screening visit was allowed. The last sample was to be conclusive)
Cardiac problems or uncontrolled treated/untreated severe hypertension (defined as systolic blood pressure higher or equal to 180 mmHg and/or diastolic blood pressure higher or equal to 100 mmHg)
Previous use of pre-mixed insulin products (pre-mixed insulin analogues or pre-mixed human preparations) or bolus insulin. Previous use of pre-mixed or bolus insulin products was allowed only in case of hospitalisation or a severe condition requiring intermittent use of pre-mixed or bolus insulin products for less than 14 consecutive days, but not during the last 3 months prior to screening visit (Visit 1)

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		Capital Federal		1405	Argentina
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25180608	Result	Gao Y, Luquez C, Lynggaard H, Andersen H, Saboo B. The SimpleMix study with biphasic insulin aspart 30: a randomized controlled trial investigating patient-driven titration versus investigator-driven titration. Curr Med Res Opin. 2014 Dec;30(12):2483-92. doi: 10.1185/03007995.2014.960512. Epub 2014 Sep 29.

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	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.

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

A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of trial product, and no later than one day after product administration. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.
BG001	Investigator-driven	The investigator performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.
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
	BG00058.9± 9.8 BG00158.0± 9.5 BG00258.5± 9.6

Gender

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00083 BG00187 BG002

Body Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00081.0± 16.2 BG00178.0± 15.0 BG002

Body Mass Index

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00029.7± 4.8 BG00129.2± 4.7 BG002

Glycosylated Haemoglobin (HbA1c)

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

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

Fasting Plasma Glucose

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0009.1± 2.7 BG0018.8± 2.8 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 in HbA1c (Glycosylated Haemoglobin) - FAS

Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in full analysis set (FAS).

Full analysis set (FAS) - analysis included endpoint derived after 20 Weeks of treatment and missing data was imputed using last observation carried forward (LOCF) where any post-baseline measurements were available. 13 subjects did not contribute to the statistical analysis after Week 20.

Posted

Least Squares Mean

Standard Error

percentage of glycosylated haemoglobin

Week 0, week 20

ID	Title	Description
OG000	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.
OG001	Investigator-driven	The investigator performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.

Units	Counts
Participants	OG000169 OG001166

Title

Denominators

Categories

Title	Measurements
	OG000-0.72± 0.08 OG001-0.97± 0.08

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	FAS	Regression, Linear	Model includes treatment, strata and region as factors and relevant baseline HbA1c as covariate.			Estimated treatment difference, Mean	0.25				95	0.04	0.46				Yes	Non-Inferiority or Equivalence	Non-inferiority for subject-driven vs. investigator driven titration would be concluded if the upper bound of the two-sided 95% CI was below or equal to 0.4%.

Primary

Change in HbA1c (Glycosylated Haemoglobin) - PP

Estimated mean change from baseline in HbA1c after 20 Weeks of treatment in per protocol (PP) analysis set.

Per protocol (PP) analysis set - analysis included subjects exposed to BIAsp 30 for more than 12 weeks without any major protocol violations. 24 subjects did not contribute to the statistical analysis after Week 20.

Posted

Least Squares Mean

Standard Error

percentage of glycosylated haemoglobin

Week 0, week 20

ID	Title	Description
OG000	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.
OG001	Investigator-driven	The investigator performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.

Secondary

Change in Fasting Plasma Glucose (FPG) (Central Laboratory Values)

Estimated mean change from baseline in FPG after 20 Weeks of treatment

Full analysis set (FAS) - analysis included endpoint derived after 20 weeks of treatment and missing data was imputed using last observation carried forward (LOCF) where any post-baseline measurements were available. 13 subjects did not contribute to the statistical analysis after Week 20.

Posted

Least Squares Mean

Standard Error

mmol/L

Week 0, week 20

ID	Title	Description
OG000	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.
OG001	Investigator-driven	The investigator performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.

Secondary

Number of Treatment Emergent Hypoglycaemic Episodes

Safety analysis set included all subjects who received at least one dose of BIAsp 30. One subject did not contribute to data.

Posted

Number

episodes

Week 0 to week 20

ID	Title	Description
OG000	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.
OG001	Investigator-driven

Secondary

Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score

From the 20 TRIM-D items, an overall score was derived. The scores were transformed to a 0 - 100 scale with higher scores indicating a better health state.

Posted

Mean

Standard Deviation

scores on a scale

Week 0

ID	Title	Description
OG000	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.
OG001	Investigator-driven	The investigator performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.

Secondary

Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score

From the 20 TRIM-D items, an overall score was derived. The scores were transformed to a 0 - 100 scale with higher scores indicating a better health state.

Posted

Mean

Standard Deviation

scores on a scale

Week 4

ID	Title	Description
OG000	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.
OG001	Investigator-driven	The investigator performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.

Secondary

Patient Reported Outcomes Evaluated: Treatment-Related Impact Measures for Diabetes (TRIM-D) - Total Score

From the 20 TRIM-D items, an overall score was derived. The scores were transformed to a 0 - 100 scale with higher scores indicating a better health state.

Posted

Mean

Standard Deviation

scores on a scale

Week 20

ID	Title	Description
OG000	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.
OG001	Investigator-driven	The investigator performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.

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	Subject-driven	The subjects performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.			2	174	0	174
EG001	Investigator-driven	The investigator performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.			3	173	0	173

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected173 at risk
Endophthalmitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected173 at risk
Pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected173 at risk
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected173 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected174 at risk EG0011 events1 affected173 at risk
Lacunar infarction	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected174 at risk EG0010 events0 affected173 at risk

ID	Term
D003920	Diabetes Mellitus
D003924	Diabetes Mellitus, Type 2

ID	Term
C557564	insulin aspart, insulin aspart protamine drug combination 30:70

The investigator performed the titration of biphasic insulin aspart 30 (BIAsp 30) dose and administered subcutaneously (under the skin) using FlexPen® twice daily for 20 weeks. The starting dose of BIAsp 30 was subject's previous basal insulin analogue dose split into two equal daily doses, immediately before breakfast and immediately before dinner. Directions for use were given to each subject at each dispensing visit. Subjects continued on their pre-trial metformin dose. Any previous basal insulin analogue and OAD (oral anti-diabetes drug) treatments (except for metformin) were discontinued. Metformin was allowed to be continued at the pre-trial dose with a total daily dose of at least 1500 mg or maximum tolerated dose (minimum 1000 mg) as prior to randomisation.

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