Trial Outcomes & Findings for Impact of Dietary Intervention on Weight Change in Subjects With Type 2 Diabetes (NCT NCT01232491)

NCT ID: NCT01232491

Last Updated: 2017-05-01

Results Overview

Estimated mean change from baseline in body weight after 26 weeks of treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 611 participants
• Primary outcome timeframe: Week 0, Week 26
• Results posted on: 2017-05-01

Participant Flow

The trial was conducted at 110 sites in 9 countries: Argentina (5), Germany (7), Poland (4), Serbia (4), Slovakia (3), Slovenia (2), Spain (4), Turkey (5) and United States of America (76).

Subjects continued on their treatment with metformin, at the pre-randomisation dose level and dosing frequency. All other oral antidiabetic drugs were discontinued before insulin detemir was used.

Participant milestones

Measure	Dietician Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Overall Study STARTED	306	305
Overall Study Exposed (Safety Analysis Set)	305	301
Overall Study COMPLETED	246	242
Overall Study NOT COMPLETED	60	63

Reasons for withdrawal

Measure	Dietician Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Overall Study Adverse Event	13	8
Overall Study Lack of Efficacy	1	5
Overall Study Protocol Violation	13	11
Overall Study Withdrawal Criteria	12	21
Overall Study Other	21	18

Baseline Characteristics

Impact of Dietary Intervention on Weight Change in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Dietician n=305 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=301 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.	Total n=606 Participants Total of all reporting groups
Age, Continuous	58.2 years STANDARD_DEVIATION 9.7 • n=5 Participants	56.5 years STANDARD_DEVIATION 10.0 • n=7 Participants	57.4 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	152 Participants n=5 Participants	143 Participants n=7 Participants	295 Participants n=5 Participants
Sex: Female, Male Male	153 Participants n=5 Participants	158 Participants n=7 Participants	311 Participants n=5 Participants
Race/Ethnicity, Customized White	274 participants n=5 Participants	268 participants n=7 Participants	542 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	21 participants n=5 Participants	26 participants n=7 Participants	47 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	5 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Oth. Pacific Islander	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Other	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	63 participants n=5 Participants	78 participants n=7 Participants	141 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	242 participants n=5 Participants	223 participants n=7 Participants	465 participants n=5 Participants
Height	1.67 meters STANDARD_DEVIATION 0.10 • n=5 Participants	1.68 meters STANDARD_DEVIATION 0.10 • n=7 Participants	1.67 meters STANDARD_DEVIATION 0.10 • n=5 Participants
Body weight	96.4 kg STANDARD_DEVIATION 18.2 • n=5 Participants	97.0 kg STANDARD_DEVIATION 20.4 • n=7 Participants	96.7 kg STANDARD_DEVIATION 19.3 • n=5 Participants
Body mass index (BMI)	34.4 kg/m^2 STANDARD_DEVIATION 5.4 • n=5 Participants	34.3 kg/m^2 STANDARD_DEVIATION 5.6 • n=7 Participants	34.4 kg/m^2 STANDARD_DEVIATION 5.5 • n=5 Participants
Duration of diabetes	8.6 years STANDARD_DEVIATION 5.8 • n=5 Participants	8.5 years STANDARD_DEVIATION 6.0 • n=7 Participants	8.6 years STANDARD_DEVIATION 5.9 • n=5 Participants
Fasting plasma glucose (FPG)	9.3 mmol/L STANDARD_DEVIATION 2.3 • n=5 Participants	9.2 mmol/L STANDARD_DEVIATION 2.0 • n=7 Participants	9.2 mmol/L STANDARD_DEVIATION 2.2 • n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.0 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.7 • n=5 Participants	7.9 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.6 • n=7 Participants	7.9 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.6 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, Week 26

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

Estimated mean change from baseline in body weight after 26 weeks of treatment.

Outcome measures

Measure	Dietician n=306 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=305 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Change From Baseline in Body Weight	-1.05 kg Standard Error 0.23	-0.56 kg Standard Error 0.23

SECONDARY outcome

Timeframe: Week 0, Week 26

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

Estimated mean change from baseline in BMI after 26 weeks of treatment.

Outcome measures

Measure	Dietician n=306 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=305 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Change From Baseline in Body Mass Index (BMI)	-0.37 kg/m^2 Standard Error 0.08	-0.20 kg/m^2 Standard Error 0.08

SECONDARY outcome

Timeframe: Week 0, Week 26

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

Estimated mean change from baseline in HbA1c after 26 weeks of treatment.

Outcome measures

Measure	Dietician n=306 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=305 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Change From Baseline in Glycosylated Haemoglobin (HbA1c)	-0.93 percentage of glycosylated haemoglobin Standard Error 0.05	-0.80 percentage of glycosylated haemoglobin Standard Error 0.05

SECONDARY outcome

Timeframe: Week 0, Week 26

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

Estimated mean change from baseline in FPG after 26 weeks of treatment.

Outcome measures

Measure	Dietician n=306 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=302 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Change From Baseline in Fasting Plasma Glucose (FPG)	-3.00 mmol/L Standard Error 0.12	-2.93 mmol/L Standard Error 0.12

SECONDARY outcome

Timeframe: Week 0 to Week 26

Population: Safety analysis set includes all subjects who received at least one dose of insulin detemir.

Corresponds to rate of adverse events (AEs) per 100 patient years of exposure. Mild AEs: no or transient symptoms, no interference with subject's daily activities. Moderate AEs: marked symptoms, moderate interference with subject's daily activities. Severe AEs: considerable interference with subject's daily activities, unacceptable. Serious AEs: AEs that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalization, persistent/significant disability/incapacity/congenital anomaly/birth defect.

Outcome measures

Measure	Dietician n=305 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=301 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Rate of Treatment Emergent Adverse Events (TEAEs) All TEAEs	387.9 rate per 100 years of patient exposure	437.1 rate per 100 years of patient exposure
Rate of Treatment Emergent Adverse Events (TEAEs) Moderate TEAEs	130.5 rate per 100 years of patient exposure	108.3 rate per 100 years of patient exposure
Rate of Treatment Emergent Adverse Events (TEAEs) Mild TEAEs	241.0 rate per 100 years of patient exposure	317.5 rate per 100 years of patient exposure
Rate of Treatment Emergent Adverse Events (TEAEs) Serious TEAEs	16.3 rate per 100 years of patient exposure	16.6 rate per 100 years of patient exposure
Rate of Treatment Emergent Adverse Events (TEAEs) Severe TEAEs	16.3 rate per 100 years of patient exposure	11.3 rate per 100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 26

Population: Safety analysis set includes all subjects who received at least one dose of insulin detemir.

Corresponds to rate of treatment emergent hypoglycaemic episodes per patient exposure year. 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. Severe, if assistance was required to actively administer carbohydrate, glucagons or other resuscitative actions.

Outcome measures

Measure	Dietician n=305 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=301 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Rate of All Treatment Emergent Hypoglycaemic Episodes Severe Events	0.01 rate per year of patient exposure	0.01 rate per year of patient exposure
Rate of All Treatment Emergent Hypoglycaemic Episodes All Events	25.47 rate per year of patient exposure	23.30 rate per year of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 26

Population: Safety analysis set includes all subjects who received at least one dose of insulin detemir.

Corresponds to rate of treatment emergent hypoglycaemic episodes per patient exposure year. 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. A hypoglycaemic episode with time of onset between 00:01 and 05:59 a.m. (both included) was considered nocturnal. Severe, if assistance was required to actively administer carbohydrate, glucagons or other resuscitative actions.

Outcome measures

Measure	Dietician n=305 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=301 Participants Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Rate of Nocturnal Treatment Emergent Hypoglycaemic Episodes All Events	5.59 rate per year of patient exposure	5.51 rate per year of patient exposure
Rate of Nocturnal Treatment Emergent Hypoglycaemic Episodes Severe Events	0.01 rate per year of patient exposure	0.01 rate per year of patient exposure

Adverse Events

Dietician

Serious events: 17 serious events

Other events: 61 other events

Deaths: 0 deaths

Control

Serious events: 19 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dietician n=305 participants at risk Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=301 participants at risk Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
Cardiac disorders Acute coronary syndrome	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Cardiac disorders Acute myocardial infarction	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.66% 2/301 • Number of events 2 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Cardiac disorders Angina pectoris	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Cardiac disorders Cardiac disorder	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Cardiac disorders Congestive cardiomyopathy	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Cardiac disorders Myocardial infarction	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Cardiac disorders Myocardial ischaemia	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Cardiac disorders Tachycardia	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Ear and labyrinth disorders Vertigo positional	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Eye disorders Retinal vein thrombosis	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Gastrointestinal disorders Gastritis	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
General disorders Chest pain	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Infections and infestations Anal abscess	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Infections and infestations Bronchitis	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Infections and infestations Bursitis infective	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Infections and infestations Lobar pneumonia	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Infections and infestations Pneumonia	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Infections and infestations Viral infection	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Injury, poisoning and procedural complications Ankle fracture	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Injury, poisoning and procedural complications Wrist fracture	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Metabolism and nutrition disorders Hypoglycaemia	0.33% 1/305 • Number of events 2 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Nervous system disorders Lumbar radiculopathy	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Nervous system disorders Migraine with aura	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Psychiatric disorders Depression	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Psychiatric disorders Schizophrenia	0.33% 1/305 • Number of events 3 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Renal and urinary disorders Calculus bladder	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.00% 0/301 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Renal and urinary disorders Calculus urinary	0.33% 1/305 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Renal and urinary disorders Nephrolithiasis	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Renal and urinary disorders Obstructive uropathy	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Reproductive system and breast disorders Endometrial hypertrophy	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.66% 2/301 • Number of events 2 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Vascular disorders Hypertension	0.00% 0/305 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	0.33% 1/301 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.

Other adverse events

Measure	Dietician n=305 participants at risk Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects received dietary consultation according to local standard during 3 face-to-face meetings and 3 phone contacts. Insulin doses were individually adjusted.	Control n=301 participants at risk Insulin detemir (Levemir®) 100 U/mL, was injected subcutaneously once daily with the evening meal or at bedtime as add-on to subject's pre-trial treatment of metformin for 26 weeks. Subjects did not receive dietary consultation except for basic dietary advice at baseline. Insulin doses were individually adjusted.
General disorders Injection site reaction	5.2% 16/305 • Number of events 21 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	4.3% 13/301 • Number of events 17 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Infections and infestations Nasopharyngitis	9.8% 30/305 • Number of events 39 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	12.6% 38/301 • Number of events 49 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Nervous system disorders Headache	7.5% 23/305 • Number of events 29 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.	8.0% 24/301 • Number of events 36 • The adverse events were collected in a time frame of 26 weeks. Safety analysis set includes all subjects who received at least one dose of insulin detemir.

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Novo Nordisk A/S

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.
• Publication restrictions are in place

Restriction type: OTHER