Effect of Different Insulin Administrations, All in Combination With Metformin, on Glycaemic Control in Subjects With Type 2 Diabetes Inadequately Controlled by Oral Anti-diabetic Drugs

Effect of 50-week Treatment With Stepwise Insulin Intensification of Basal-bolus Insulin Analogues (Insulin Detemir and Aspart) or Biphasic Insulin Aspart 30 (NovoMix 30) All in Combination With Fixed Dose of Metformin on Glycaemic Control (Measured as HbA1c) in Subjects With Type 2 Diabetes. Open Labelled, Randomized, Two-arm, Parallel Group, Multi-centre, Multi-national Trial

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01068652

Enrollment

403

Registered

2010-02-15

Start date

2010-03-31

Completion date

2012-05-31

Last updated

2017-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes, Diabetes Mellitus, Type 2

Brief summary

This trial is conducted in Africa. The aim of this clinical trial is to investigate the effect of 50 weeks of treatment with different intensified insulin administrations (all in combination with a fixed dose of metformin) on blood sugar control in subjects with type 2 diabetes inadequately controlled by oral anti-diabetic drugs (OADs).

Interventions

DRUGinsulin detemir

Initial dose of 0.1 U/kg once daily, injected s.c. (under the skin).

DRUGinsulin aspart

Pending evaluation of HbA1c every 3 months, insulin aspart was added to the insulin detemir treatment (up to three does daily, injected s.c. (under the skin)

DRUGbiphasic insulin aspart 30

Initial dose of 0.1 U/kg once daily, injected s.c. (under the skin). Pending evaluation of HbA1c every 3 months, the dose will intensified up to 3 doses daily

DRUGmetformin

1000-2000 mg/day in combination with insulin treatment

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject) * Diagnosed type 2 diabetes (WHO 1999 criteria) * Currently treated with suboptimal daily dose of OADs (mono or combination therapy) for at least 6 months * Male or female age at least 18 years old * HbA1c at least 7.0 % and maximum 11.0% for subjects treated with metformin mono-therapy, or maximum 10% for subjects treated with OAD combination therapy * BMI maximum 40 kg/m\^2 * Able and willing to perform self-monitoring of plasma glucose according to the protocol and to keep a diary * Able and willing to be treated with up to 4 insulin injections per day

Exclusion criteria

* Known or suspected allergy to trial product(s) or related products * Previous participation in this trial. Participation is defined as randomisation * Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice) * Participated in another clinical trial and received an investigational drug within the last weeks prior to the present trial * Impaired hepatic function defined as alanine aminotransferase (ALT) or alkaline phosphatase (ALP) at least 2.5 times upper referenced limit * Impaired renal function defined as serum-creatinine at least 1.3 mg/dL (at least 115 mmol/L) for males and at least 1.2 mg/dL (at least 106 mmol/L) for females * Subject has a clinically significant, active (or over the past 12 months) cardiovascular history (including a history of myocardial infarction (MI), arrhythmias or conduction delays on ECG, unstable angina, or decompensated heart failure (New York Heart Association class III and IV) * Severe uncontrolled treated or untreated hypertension (sitting systolic blood pressure at least 180 mmHg or sitting diastolic blood pressure at least 100 mmHg) * Proliferative retinopathy or macular oedema requiring acute treatment * Metformin contraindications according to the package insert * Current treatment with systemic corticosteroids * Subject has a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject * Current addiction to alcohol or other addictive substances as determined by the Investigator * Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation in the study or use of the glucose monitor * History of hypoglycaemic unawareness and/or two or more severe hypoglycaemic episodes in the past year as judged by the Investigator

Design outcomes

Primary

Measure	Time frame	Description
Glycosylated Haemoglobin (HbA1c)	Week 50	Estimated mean difference in HbA1c after 50 weeks of treatment

Secondary

Measure	Time frame	Description
Change in Glycosylated Haemoglobin (HbA1c) After 14 Weeks of Treatment	Week 0, Week 14	Observed mean change from baseline in HbA1c at Week 14 (visit 11)
Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment	Week 0, Week 26	Observed mean change in from baseline in HbA1c at Week 26 (visit 18)
Change in Glycosylated Haemoglobin (HbA1c) After 38 Weeks of Treatment	Week 0, Week 38	Observed mean change from baseline in HbA1c at Week 38 (visit 25)
Change in Glycosylated Haemoglobin (HbA1c) at Week 50	Week 0, Week 50	Observed mean change from baseline in HbA1c at Week 50 (visit 32)
Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 14 Weeks of Treatment	Week 14	Number of subjects achieving HbA1c below 7.0% after 14 weeks of treatment (visit 11)
Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 26 Weeks of Treatment	Week 26	Number of subjects achieving HbA1c below 7.0% after 26 weeks of treatment (visit 18)
Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 38 Weeks of Treatment	Week 38	Number of subjects achieving HbA1c below 7.0% after 38 weeks of treatment (visit 25)
Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 50 Weeks of Treatment	Week 50	Number of subjects achieving HbA1c below 7.0% after 50 weeks of treatment (visit 32)
Mean of Prandial Plasma Glucose (PG) Increment After 26 Weeks of Treatment	Week 26	Observed overall mean of PG increment after 26 weeks of treatment (visit 18). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}
Mean of Prandial Plasma Glucose (PG) Increment After 38 Weeks of Treatment	Week 38	Observed overall mean of PG increment after 38 weeks of treatment (visit 25). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}.
Mean of Prandial Plasma Glucose (PG) Increment After 50 Weeks of Treatment	Week 50	Observed overall mean of PG increment after 50 weeks of treatment (visit 32). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}.
Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Week 14	Observed overall mean of 8-point PG profile after 14 weeks of treatment (visit 11)
Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Week 26	Observed overall mean of 8-point PG profile after 26 weeks of treatment (visit 18)
Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Week 38	Observed overall mean of 8-point PG profile after 38 weeks of treatment (visit 25)
Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Week 50	Observed overall mean of 8-point PG profile after 50 weeks of treatment (visit 32)
Mean of Prandial Plasma Glucose (PG) Increment After 14 Weeks of Treatment	Week 14	Observed overall mean of PG increment after 14 weeks of treatment (Visit 11). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}

Countries

Algeria, Egypt, Morocco, South Africa, Tunisia

Participant flow

Recruitment details

The trial was conducted at 23 sites in 4 countries: Egypt (1), Algeria (9), Tunisia (4) and South Africa (9). The trial consisted of two weeks of screening, three weeks of run-in, and 50 weeks of treatment.

Participants by arm

Arm	Count
Detemir + Met Individually adjusted insulin detemir (Detemir) was given subcutaneoulsy (s.c.) at bedtime in the thigh at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, individually adjusted insulin aspart was added to the insulin detemir treatment (up to three doses daily for maximum 36 weeks, injected s.c. \[under the skin\]) if treatment target of HbA1c below 7.0% was not reached.	200
BIAsp 30 + Met Individually adjusted biphasic insulin aspart 30 (BIAsp 30) was given subcutaneously (s.c.) in the abdomen at dinner at an initial dose of 0.1 U/kg once daily for 50 weeks in combination with 1000-2000 mg/day metformin (Met). Pending evaluation of HbA1c every 3 months, the dose was intensified up to 3 doses daily, injected s.c. (under the skin) if treatment target of HbA1c below 7.0% was not reached.	203
Total	403

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	4	0
Overall Study	Lack of Efficacy	0	2
Overall Study	Lost to Follow-up	2	1
Overall Study	Patient was not eligible	1	0
Overall Study	Protocol Violation	3	6
Overall Study	Unclassified	7	4
Overall Study	Withdrawal criteria	1	2

Baseline characteristics

Characteristic	Detemir + Met	BIAsp 30 + Met	Total
Age, Continuous	53.0 years STANDARD_DEVIATION 9	52.6 years STANDARD_DEVIATION 10.1	52.8 years STANDARD_DEVIATION 9.6
Gender Female	113 Participants	128 Participants	241 Participants
Gender Male	87 Participants	75 Participants	162 Participants
Glycosylated haemoglobin (HbA1c)	8.6 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1	8.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1	8.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1
Race/Ethnicity, Customized Asian	16 participants	21 participants	37 participants
Race/Ethnicity, Customized Black or African American	18 participants	11 participants	29 participants
Race/Ethnicity, Customized Other	112 participants	113 participants	225 participants
Race/Ethnicity, Customized White	54 participants	58 participants	112 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	75 / 200	78 / 203
serious Total, serious adverse events	13 / 200	7 / 203

Outcome results

Primary

Glycosylated Haemoglobin (HbA1c)

Estimated mean difference in HbA1c after 50 weeks of treatment

Time frame: Week 50

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF). For 20 subjects, HbA1c values were missing.

Arm	Measure	Value (MEAN)	Dispersion
Detemir + Met	Glycosylated Haemoglobin (HbA1c)	7.34 percentage of glycosylated haemoglobin	Standard Error 0.13
BIAsp 30 + Met	Glycosylated Haemoglobin (HbA1c)	7.23 percentage of glycosylated haemoglobin	Standard Error 0.12

Comparison: To investigate the effect of different treatments, an analysis of covariance (ANCOVA) model was used to analyse HbA1c at week 50 with treatment group (2 categories: insulin detemir and aspart; BIAsp 30), country and pre-trial OAD(s) treatment (one OAD vs. more OADs) as factors and HbA1c at baseline (week 0) as a covariate. The treatment difference was estimated and a 95% confidence interval (CI) for the difference was calculated.p-value: 0.340695% CI: [-0.12, 0.34]ANCOVA

Secondary

Change in Glycosylated Haemoglobin (HbA1c) After 14 Weeks of Treatment

Observed mean change from baseline in HbA1c at Week 14 (visit 11)

Time frame: Week 0, Week 14

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF). For 20 subjects, values for change in HbA1c were missing.

Arm	Measure	Value (MEAN)	Dispersion
Detemir + Met	Change in Glycosylated Haemoglobin (HbA1c) After 14 Weeks of Treatment	-0.18 percentage of glycosylated haemoglobin	Standard Deviation 1.16
BIAsp 30 + Met	Change in Glycosylated Haemoglobin (HbA1c) After 14 Weeks of Treatment	-0.64 percentage of glycosylated haemoglobin	Standard Deviation 1.12

Secondary

Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment

Observed mean change in from baseline in HbA1c at Week 26 (visit 18)

Time frame: Week 0, Week 26

Arm	Measure	Value (MEAN)	Dispersion
Detemir + Met	Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment	-1.05 percentage of glycosylated haemoglobin	Standard Deviation 1.05
BIAsp 30 + Met	Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment	-1.30 percentage of glycosylated haemoglobin	Standard Deviation 1.28

Secondary

Change in Glycosylated Haemoglobin (HbA1c) After 38 Weeks of Treatment

Observed mean change from baseline in HbA1c at Week 38 (visit 25)

Time frame: Week 0, Week 38

Arm	Measure	Value (MEAN)	Dispersion
Detemir + Met	Change in Glycosylated Haemoglobin (HbA1c) After 38 Weeks of Treatment	-1.35 percentage of glycosylated haemoglobin	Standard Deviation 1.16
BIAsp 30 + Met	Change in Glycosylated Haemoglobin (HbA1c) After 38 Weeks of Treatment	-1.56 percentage of glycosylated haemoglobin	Standard Deviation 1.39

Secondary

Change in Glycosylated Haemoglobin (HbA1c) at Week 50

Observed mean change from baseline in HbA1c at Week 50 (visit 32)

Time frame: Week 0, Week 50

Arm	Measure	Value (MEAN)	Dispersion
Detemir + Met	Change in Glycosylated Haemoglobin (HbA1c) at Week 50	-1.16 percentage of glycosylated haemoglobin	Standard Deviation 1.33
BIAsp 30 + Met	Change in Glycosylated Haemoglobin (HbA1c) at Week 50	-1.34 percentage of glycosylated haemoglobin	Standard Deviation 1.4

Secondary

Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment

Observed overall mean of 8-point PG profile after 14 weeks of treatment (visit 11)

Time frame: Week 14

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF).

Arm	Measure	Group	Value (MEAN)	Dispersion
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Before Breakfast (n=193, 194)	136.44 mg/dL	Standard Deviation 42.86
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	120 min After Breakfast (n=187, 184)	181.89 mg/dL	Standard Deviation 54.42
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Before Lunch (n=192, 193)	157.61 mg/dL	Standard Deviation 53.43
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	120 min After Lunch (n=186, 185)	199.40 mg/dL	Standard Deviation 64.38
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Before Dinner (n=191, 192)	169.69 mg/dL	Standard Deviation 54.91
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	120 min After Dinner (n=183, 185)	212.23 mg/dL	Standard Deviation 61.45
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Bedtime (n=187, 192)	200.15 mg/dL	Standard Deviation 60.83
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	At 2 AM - 3 AM (n=172, 177)	158.69 mg/dL	Standard Deviation 50.06
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	At 2 AM - 3 AM (n=172, 177)	139.93 mg/dL	Standard Deviation 43.39
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Before Breakfast (n=193, 194)	128.31 mg/dL	Standard Deviation 33.58
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Before Dinner (n=191, 192)	168.09 mg/dL	Standard Deviation 59.58
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	120 min After Breakfast (n=187, 184)	176.31 mg/dL	Standard Deviation 44.5
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Bedtime (n=187, 192)	156.65 mg/dL	Standard Deviation 50.65
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	Before Lunch (n=192, 193)	156.12 mg/dL	Standard Deviation 51.57
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	120 min After Dinner (n=183, 185)	173.95 mg/dL	Standard Deviation 54.86
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment	120 min After Lunch (n=186, 185)	199.75 mg/dL	Standard Deviation 59.04

Secondary

Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment

Observed overall mean of 8-point PG profile after 26 weeks of treatment (visit 18)

Time frame: Week 26

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF).

Arm	Measure	Group	Value (MEAN)	Dispersion
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Before Breakfast (n=193, 194)	116.57 mg/dL	Standard Deviation 34.4
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	120 min After Breakfast (n=191, 191)	163.52 mg/dL	Standard Deviation 50.02
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Before Lunch (n=193, 194)	140.97 mg/dL	Standard Deviation 49.96
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	120 min After Lunch (n=191, 191)	166.00 mg/dL	Standard Deviation 57.15
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Before Dinner (n=192, 194)	147.58 mg/dL	Standard Deviation 48.9
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	120 min After Dinner (n=188, 191)	172.21 mg/dL	Standard Deviation 57.34
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Bedtime (n=190, 194)	164.70 mg/dL	Standard Deviation 63.68
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	At 2 AM - 3 AM (n=181, 187)	133.59 mg/dL	Standard Deviation 47.54
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	At 2 AM - 3 AM (n=181, 187)	123.29 mg/dL	Standard Deviation 35.16
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Before Breakfast (n=193, 194)	115.79 mg/dL	Standard Deviation 27.23
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Before Dinner (n=192, 194)	143.29 mg/dL	Standard Deviation 45.5
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	120 min After Breakfast (n=191, 191)	153.85 mg/dL	Standard Deviation 42.68
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Bedtime (n=190, 194)	140.39 mg/dL	Standard Deviation 42.71
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	Before Lunch (n=193, 194)	131.27 mg/dL	Standard Deviation 42.85
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	120 min After Dinner (n=188, 191)	152.44 mg/dL	Standard Deviation 45.53
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment	120 min After Lunch (n=191, 191)	178.92 mg/dL	Standard Deviation 51.14

Secondary

Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment

Observed overall mean of 8-point PG profile after 38 weeks of treatment (visit 25)

Time frame: Week 38

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF).

Arm	Measure	Group	Value (MEAN)	Dispersion
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Before Breakfast (n=193, 194)	110.14 mg/dL	Standard Deviation 30.64
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	120 min After Breakfast (n=191, 192)	146.70 mg/dL	Standard Deviation 44.11
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Before Lunch (n=193, 194)	130.63 mg/dL	Standard Deviation 42.17
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	120 min After Lunch (n=191, 192)	145.91 mg/dL	Standard Deviation 51.38
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Before Dinner (n=193, 194)	132.26 mg/dL	Standard Deviation 41.9
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	120 min After Dinner (n=192,192)	155.47 mg/dL	Standard Deviation 49.09
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Bedtime (n=193, 194)	146.37 mg/dL	Standard Deviation 51.58
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	At 2 AM - 3 AM (n=187, 190)	124.57 mg/dL	Standard Deviation 42.11
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	At 2 AM - 3 AM (n=187, 190)	117.42 mg/dL	Standard Deviation 35.6
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Before Breakfast (n=193, 194)	110.86 mg/dL	Standard Deviation 27.11
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Before Dinner (n=193, 194)	129.10 mg/dL	Standard Deviation 43.84
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	120 min After Breakfast (n=191, 192)	139.38 mg/dL	Standard Deviation 42.74
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Bedtime (n=193, 194)	132.45 mg/dL	Standard Deviation 43.54
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	Before Lunch (n=193, 194)	118.30 mg/dL	Standard Deviation 40.28
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	120 min After Dinner (n=192,192)	142.82 mg/dL	Standard Deviation 50.47
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment	120 min After Lunch (n=191, 192)	158.45 mg/dL	Standard Deviation 47.7

Secondary

Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment

Observed overall mean of 8-point PG profile after 50 weeks of treatment (visit 32)

Time frame: Week 50

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF).

Arm	Measure	Group	Value (MEAN)	Dispersion
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Before Breakfast (n=193, 194)	108.78 mg/dL	Standard Deviation 31.1
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	120 min After Breakfast (n=191, 192)	140.05 mg/dL	Standard Deviation 40.98
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Before Lunch (n=193, 194)	120.43 mg/dL	Standard Deviation 37.62
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	120 min After Lunch (n=191, 192)	139.48 mg/dL	Standard Deviation 49.03
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Before Dinner (n=193, 194)	128.28 mg/dL	Standard Deviation 40.63
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	120 min After Dinner (n=192, 192)	144.19 mg/dL	Standard Deviation 49.24
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Bedtime (n=193, 194)	137.13 mg/dL	Standard Deviation 51.18
Detemir + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	At 2 AM - 3 AM (n=187, 190)	118.60 mg/dL	Standard Deviation 40.65
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	At 2 AM - 3 AM (n=187, 190)	113.14 mg/dL	Standard Deviation 35.21
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Before Breakfast (n=193, 194)	110.76 mg/dL	Standard Deviation 22.08
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Before Dinner (n=193, 194)	126.76 mg/dL	Standard Deviation 40.16
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	120 min After Breakfast (n=191, 192)	132.45 mg/dL	Standard Deviation 35.55
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Bedtime (n=193, 194)	130.10 mg/dL	Standard Deviation 43.08
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	Before Lunch (n=193, 194)	115.02 mg/dL	Standard Deviation 36.2
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	120 min After Dinner (n=192, 192)	138.08 mg/dL	Standard Deviation 42.11
BIAsp 30 + Met	Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment	120 min After Lunch (n=191, 192)	149.90 mg/dL	Standard Deviation 44.32

Secondary

Mean of Prandial Plasma Glucose (PG) Increment After 14 Weeks of Treatment

Observed overall mean of PG increment after 14 weeks of treatment (Visit 11). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}

Time frame: Week 14

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF). For 28 subjects, PG (mg/dL) increment values were missing at all evaluations.

Arm	Measure	Value (MEAN)	Dispersion
Detemir + Met	Mean of Prandial Plasma Glucose (PG) Increment After 14 Weeks of Treatment	43.19 mg/dL	Standard Deviation 33.64
BIAsp 30 + Met	Mean of Prandial Plasma Glucose (PG) Increment After 14 Weeks of Treatment	32.61 mg/dL	Standard Deviation 31.99

Secondary

Mean of Prandial Plasma Glucose (PG) Increment After 26 Weeks of Treatment

Observed overall mean of PG increment after 26 weeks of treatment (visit 18). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}

Time frame: Week 26

Population: Full analysis set (FAS) includes all randomised subjects and missing data is imputed using last observation carried forward (LOCF). For 19 subjects, PG (mg/dL) increment values were missing at all evaluations.

Arm	Measure	Value (MEAN)	Dispersion
Detemir + Met	Mean of Prandial Plasma Glucose (PG) Increment After 26 Weeks of Treatment	32.95 mg/dL	Standard Deviation 30.25
BIAsp 30 + Met	Mean of Prandial Plasma Glucose (PG) Increment After 26 Weeks of Treatment	31.71 mg/dL	Standard Deviation 27.86

Secondary

Mean of Prandial Plasma Glucose (PG) Increment After 38 Weeks of Treatment

Observed overall mean of PG increment after 38 weeks of treatment (visit 25). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}.

Time frame: Week 38

Arm	Measure	Value (MEAN)	Dispersion
Detemir + Met	Mean of Prandial Plasma Glucose (PG) Increment After 38 Weeks of Treatment	25.44 mg/dL	Standard Deviation 27.95
BIAsp 30 + Met	Mean of Prandial Plasma Glucose (PG) Increment After 38 Weeks of Treatment	28.32 mg/dL	Standard Deviation 30.69

Secondary

Mean of Prandial Plasma Glucose (PG) Increment After 50 Weeks of Treatment

Observed overall mean of PG increment after 50 weeks of treatment (visit 32). Mean PG Increment was calculated using the average of difference between the Post Prandial and Pre Prandial Glucose values {ie .average of (Post Breakfast - Pre Breakfast), (Post Lunch - Pre Lunch) and (Post Dinner - Pre Dinner)}.

Time frame: Week 50

Arm	Measure	Value (MEAN)	Dispersion
Detemir + Met	Mean of Prandial Plasma Glucose (PG) Increment After 50 Weeks of Treatment	22.45 mg/dL	Standard Deviation 25.5
BIAsp 30 + Met	Mean of Prandial Plasma Glucose (PG) Increment After 50 Weeks of Treatment	23.66 mg/dL	Standard Deviation 28.91

Secondary

Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 14 Weeks of Treatment

Number of subjects achieving HbA1c below 7.0% after 14 weeks of treatment (visit 11)

Time frame: Week 14

Population: Full Analysis Set (FAS) includes all randomised subjects. For 20 subjects, values were missing.

Arm	Measure	Value (NUMBER)
Detemir + Met	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 14 Weeks of Treatment	15 Subjects
BIAsp 30 + Met	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 14 Weeks of Treatment	26 Subjects

Secondary

Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 26 Weeks of Treatment

Number of subjects achieving HbA1c below 7.0% after 26 weeks of treatment (visit 18)

Time frame: Week 26

Population: Full Analysis Set (FAS) includes all randomised subjects. For 29 subjects, values were missing.

Arm	Measure	Value (NUMBER)
Detemir + Met	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 26 Weeks of Treatment	67 Subjects
BIAsp 30 + Met	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 26 Weeks of Treatment	77 Subjects

Secondary

Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 38 Weeks of Treatment

Number of subjects achieving HbA1c below 7.0% after 38 weeks of treatment (visit 25)

Time frame: Week 38

Population: Full Analysis Set (FAS) includes all randomised subjects. For 31 subjects, values were missing.

Arm	Measure	Value (NUMBER)
Detemir + Met	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 38 Weeks of Treatment	84 Subjects
BIAsp 30 + Met	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 38 Weeks of Treatment	103 Subjects

Secondary

Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 50 Weeks of Treatment

Number of subjects achieving HbA1c below 7.0% after 50 weeks of treatment (visit 32)

Time frame: Week 50

Population: Full Analysis Set (FAS) includes all randomised subjects. For 35 subjects, values were missing.

Arm	Measure	Value (NUMBER)
Detemir + Met	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 50 Weeks of Treatment	73 Subjects
BIAsp 30 + Met	Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 50 Weeks of Treatment	84 Subjects

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Effect of Different Insulin Administrations, All in Combination With Metformin, on Glycaemic Control in Subjects With Type 2 Diabetes Inadequately Controlled by Oral Anti-diabetic Drugs

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Glycosylated Haemoglobin (HbA1c)

Change in Glycosylated Haemoglobin (HbA1c) After 14 Weeks of Treatment

Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment

Change in Glycosylated Haemoglobin (HbA1c) After 38 Weeks of Treatment

Change in Glycosylated Haemoglobin (HbA1c) at Week 50

Mean of 8-point Plasma Glucose (PG) Profile After 14 Weeks of Treatment

Mean of 8-point Plasma Glucose (PG) Profile After 26 Weeks of Treatment

Mean of 8-point Plasma Glucose (PG) Profile After 38 Weeks of Treatment

Mean of 8-point Plasma Glucose (PG) Profile After 50 Weeks of Treatment

Mean of Prandial Plasma Glucose (PG) Increment After 14 Weeks of Treatment

Mean of Prandial Plasma Glucose (PG) Increment After 26 Weeks of Treatment

Mean of Prandial Plasma Glucose (PG) Increment After 38 Weeks of Treatment

Mean of Prandial Plasma Glucose (PG) Increment After 50 Weeks of Treatment

Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 14 Weeks of Treatment

Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 26 Weeks of Treatment

Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 38 Weeks of Treatment

Number of Subjects Achieving Glycosylated Haemoglobin (HbA1c) Below 7.0% After 50 Weeks of Treatment