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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01232491
• Collaborator: (none)
• Enrollment: 611
• Locations: 112
• Arms: 2
• Actual Duration (Months): 12.5
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This trial is conducted in Europe, and North and South America. The aim of this trial is to investigate if a dietary intervention has an effect on weight when initiating insulin treatment in subjects with type 2 diabetes currently treated with oral antidiabetic drugs (OADs).

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: Insulin detemir; Dietary Supplement: Dietary regimen	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 611 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 26-week Randomised, Controlled, Open Label, Multicentre, Multinational, Treat to Target Trial Investigating the Impact of Dietary Intervention on Weight Change and the Relationship Between Weight Change and Baseline Body Mass Index (BMI) in Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetic Drugs (OADs) Initiating Insulin Therapy With Insulin Detemir in Combination With Metformin (Levemir DIET)
• Actual Study Start Date: Oct 29, 2010
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 14, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Insulin detemir; Individually adjusted insulin detemir subcutaneously (under the skin) once daily. Subjects continue their pre-trial metformin treatment.
Experimental: 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.	Drug: Insulin detemir; Individually adjusted insulin detemir subcutaneously (under the skin) once daily. Subjects continue their pre-trial metformin treatment.; Dietary Supplement: Dietary regimen; Subjects receive dietary consultation by a dietician at six occasions during the trial.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Body Weight [Week 0, Week 26]

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

Secondary Outcome Measures

1. Change From Baseline in Body Mass Index (BMI) [Week 0, Week 26]

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

2. Change From Baseline in Glycosylated Haemoglobin (HbA1c) [Week 0, Week 26]

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

3. Change From Baseline in Fasting Plasma Glucose (FPG) [Week 0, Week 26]

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

4. Rate of Treatment Emergent Adverse Events (TEAEs) [Week 0 to Week 26]

   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.

5. Rate of All Treatment Emergent Hypoglycaemic Episodes [Week 0 to Week 26]

   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.

6. Rate of Nocturnal Treatment Emergent Hypoglycaemic Episodes [Week 0 to Week 26]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes (diagnosed clinically) for at least 6 months prior trial start

• Insulin naive subjects

• HbA1c: 7.0-9.0 % (both inclusive)

• Body Mass Index (BMI): 25.0-45.0 kg/m^2 (both inclusive)

Exclusion Criteria:

• Use of Thiazolidinedione (TZDs) or Glucagon-like peptide-1 analogue (GLP- 1) receptor agonists within the last 3 months prior to trial enrollment

• Cardiovascular disease within the last 6 months

• Recurrent severe hypoglycaemia or hypoglycaemic unawareness or hospitalisation for diabetic ketoacidosis during the previous 6 months

• Uncontrolled treated/untreated severe hypertension, impaired liver function, impaired renal function, known proliferative retinopathy or maculopathy requiring treatment

• Cancer and medical history of cancer in the past 5 years (except basal cell skin cancer or squamous cell skin cancer)

• Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35233
2	Novo Nordisk Investigational Site	Ozark	Alabama	United States	36360
3	Novo Nordisk Investigational Site	Anaheim	California	United States	92801
4	Novo Nordisk Investigational Site	Burlingame	California	United States	94010
5	Novo Nordisk Investigational Site	Concord	California	United States	94520
6	Novo Nordisk Investigational Site	Fullerton	California	United States	92835
7	Novo Nordisk Investigational Site	Long Beach	California	United States	90806
8	Novo Nordisk Investigational Site	Long Beach	California	United States	90807
9	Novo Nordisk Investigational Site	Long Beach	California	United States	90822
10	Novo Nordisk Investigational Site	Montclair	California	United States	91763
11	Novo Nordisk Investigational Site	National City	California	United States	91950
12	Novo Nordisk Investigational Site	Redlands	California	United States	92374
13	Novo Nordisk Investigational Site	Santa Ana	California	United States	92705
14	Novo Nordisk Investigational Site	Spring Valley	California	United States	91978
15	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
16	Novo Nordisk Investigational Site	Colorado Springs	Colorado	United States	80907
17	Novo Nordisk Investigational Site	Norwalk	Connecticut	United States	06851
18	Novo Nordisk Investigational Site	Bradenton	Florida	United States	34201
19	Novo Nordisk Investigational Site	Clearwater	Florida	United States	33765
20	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32204
21	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32207
22	Novo Nordisk Investigational Site	Jupiter	Florida	United States	33458
23	Novo Nordisk Investigational Site	Miami	Florida	United States	33135
24	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33027
25	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33028
26	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33029
27	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30342
28	Novo Nordisk Investigational Site	Perry	Georgia	United States	31069
29	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
30	Novo Nordisk Investigational Site	Oympiafields	Illinois	United States	60641
31	Novo Nordisk Investigational Site	Evansville	Indiana	United States	47714
32	Novo Nordisk Investigational Site	Shawnee Mission	Kansas	United States	66204
33	Novo Nordisk Investigational Site	Topeka	Kansas	United States	66606
34	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
35	Novo Nordisk Investigational Site	Portland	Maine	United States	04101
36	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
37	Novo Nordisk Investigational Site	Brockton	Massachusetts	United States	02301
38	Novo Nordisk Investigational Site	Buckley	Michigan	United States	49620
39	Novo Nordisk Investigational Site	Southfield	Michigan	United States	48034
40	Novo Nordisk Investigational Site	St. Louis	Missouri	United States	63141
41	Novo Nordisk Investigational Site	Berlin	New Jersey	United States	08009
42	Novo Nordisk Investigational Site	New York	New York	United States	10025
43	Novo Nordisk Investigational Site	Northport	New York	United States	11768
44	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
45	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28277
46	Novo Nordisk Investigational Site	Durham	North Carolina	United States	27710
47	Novo Nordisk Investigational Site	Raleigh	North Carolina	United States	27609
48	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
49	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45245
50	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45406
51	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45439
52	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73103
53	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73104-5020
54	Novo Nordisk Investigational Site	Altoona	Pennsylvania	United States	16602
55	Novo Nordisk Investigational Site	Jenkintown	Pennsylvania	United States	19046
56	Novo Nordisk Investigational Site	Norristown	Pennsylvania	United States	19401
57	Novo Nordisk Investigational Site	Anderson	South Carolina	United States	29621
58	Novo Nordisk Investigational Site	Greer	South Carolina	United States	29651
59	Novo Nordisk Investigational Site	Rapid City	South Dakota	United States	57701
60	Novo Nordisk Investigational Site	Bristol	Tennessee	United States	37620-7352
61	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37411
62	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
63	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37212
64	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
65	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
66	Novo Nordisk Investigational Site	Dallas	Texas	United States	75251
67	Novo Nordisk Investigational Site	Odessa	Texas	United States	79761
68	Novo Nordisk Investigational Site	Plano	Texas	United States	75075
69	Novo Nordisk Investigational Site	St. George	Utah	United States	84790
70	Novo Nordisk Investigational Site	Norfolk	Virginia	United States	23502
71	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23249
72	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23294
73	Novo Nordisk Investigational Site	Winchester	Virginia	United States	22601
74	Novo Nordisk Investigational Site	Spokane	Washington	United States	99208
75	Novo Nordisk Investigational Site	Martinsburg	West Virginia	United States	25401
76	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53209
77	Novo Nordisk Investigational Site	Buenos Aires		Argentina	B1636DSU
78	Novo Nordisk Investigational Site	Caba		Argentina	C1419AHN
79	Novo Nordisk Investigational Site	Capital Federal		Argentina	1429
80	Novo Nordisk Investigational Site	Córdoba		Argentina	5000
81	Novo Nordisk Investigational Site	Godoy Cruz		Argentina	M5501ARP
82	Novo Nordisk Investigational Site	Bad Neuenahr-Ahrweiler		Germany	53474
83	Novo Nordisk Investigational Site	Gelnhausen		Germany	63571
84	Novo Nordisk Investigational Site	Mainz		Germany	55116
85	Novo Nordisk Investigational Site	Marburg		Germany	35039
86	Novo Nordisk Investigational Site	Rehlingen-Siersburg		Germany	66780
87	Novo Nordisk Investigational Site	St. Ingbert		Germany	66386
88	Novo Nordisk Investigational Site	Völklingen		Germany	66333
89	Novo Nordisk Investigational Site	Bialystok		Poland	15-445
90	Novo Nordisk Investigational Site	Lublin		Poland	20-044
91	Novo Nordisk Investigational Site	Torun		Poland	87-100
92	Novo Nordisk Investigational Site	Warszawa		Poland	00-911
93	Novo Nordisk Investigational Site	Carolina		Puerto Rico	00983
94	Novo Nordisk Investigational Site	Manati		Puerto Rico	00674
95	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194358
96	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	195213
97	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	199034
98	Novo Nordisk Investigational Site	Belgrade		Serbia	11000
99	Novo Nordisk Investigational Site	Bratislava		Slovakia	851 01
100	Novo Nordisk Investigational Site	Kosice		Slovakia	04-001
101	Novo Nordisk Investigational Site	Lubochna		Slovakia	03491
102	Novo Nordisk Investigational Site	Koper		Slovenia	SI-6000
103	Novo Nordisk Investigational Site	Maribor		Slovenia	2000
104	Novo Nordisk Investigational Site	Novo mesto		Slovenia	8000
105	Novo Nordisk Investigational Site	Málaga		Spain	29006
106	Novo Nordisk Investigational Site	Málaga		Spain	29009
107	Novo Nordisk Investigational Site	Sanlúcar de Barrameda		Spain	11540
108	Novo Nordisk Investigational Site	Ankara		Turkey	06110
109	Novo Nordisk Investigational Site	Istanbul		Turkey	34096
110	Novo Nordisk Investigational Site	Istanbul		Turkey	34098
111	Novo Nordisk Investigational Site	Istanbul		Turkey	34722
112	Novo Nordisk Investigational Site	Samsun		Turkey	55139

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry Gorsøe (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

• Niswender K, Piletic M, Andersen H, Conradsen Hiort L, Hollander P. Weight change upon once-daily initiation of insulin detemir with or without dietary intervention in overweight or obese insulin-naïve individuals with type 2 diabetes: results from the DIET trial. Diabetes Obes Metab. 2014 Feb;16(2):186-92. doi: 10.1111/dom.12218. Epub 2013 Oct 29.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01232491
• Other Study ID Numbers: NN304-3785; U1111-1116-2629; 2009-014894-42
• First Posted: Nov 2, 2010
• Last Update Posted: May 1, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Body Weight Changes; Insulin Detemir

Study Results

Participant Flow

Recruitment Details	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).
Pre-assignment Detail	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.

Arm/Group Title	Dietician	Control
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	306	305
Exposed (Safety Analysis Set)	305	301
COMPLETED	246	242
NOT COMPLETED	60	63

Baseline Characteristics

Arm/Group Title	Dietician	Control	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	305	301	606
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.2 (9.7)	56.5 (10.0)	57.4 (9.9)
Sex: Female, Male (Count of Participants)
Female	152 49.8%	143 47.5%	295 48.7%
Male	153 50.2%	158 52.5%	311 51.3%
Race/Ethnicity, Customized (participants) [Number]
White	274 89.8%	268 89%	542 89.4%
Black or African American	21 6.9%	26 8.6%	47 7.8%
Asian	2 0.7%	5 1.7%	7 1.2%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Native Hawaiian or Oth. Pacific Islander	3 1%	0 0%	3 0.5%
Other	5 1.6%	2 0.7%	7 1.2%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	63 20.7%	78 25.9%	141 23.3%
Not Hispanic or Latino	242 79.3%	223 74.1%	465 76.7%
Height (meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters]	1.67 (0.10)	1.68 (0.10)	1.67 (0.10)
Body weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	96.4 (18.2)	97.0 (20.4)	96.7 (19.3)
Body mass index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	34.4 (5.4)	34.3 (5.6)	34.4 (5.5)
Duration of diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.6 (5.8)	8.5 (6.0)	8.6 (5.9)
Fasting plasma glucose (FPG) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	9.3 (2.3)	9.2 (2.0)	9.2 (2.2)
Glycosylated haemoglobin (HbA1c) (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	8.0 (0.7)	7.9 (0.6)	7.9 (0.6)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Body Weight
Description	Estimated mean change from baseline in body weight after 26 weeks of treatment.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dietician	Control
Arm/Group Description	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.	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.
Measure Participants	306	305
Least Squares Mean (Standard Error) [kg]	-1.05 (0.23)	-0.56 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietician, Control
	Comments	Normal linear regression model with treatment, strata, use of insulin secretagogue at screening, sex and region as factors and age and weight at baseline as covariates. Superiority was considered confirmed if the upper bound of the two-sided 95% CI for the estimated treatment difference (dietary intervention versus no dietary intervention), which was calculated using the FAS, was below 0 kg.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.132
	Comments	If the p-value for the two-sided test was less than 5%, and D (the estimated treatment difference [dietary intervention versus no dietary intervention]) was less than 0 then superiority for dietary intervention was considered confirmed.
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	0.49
	Confidence Interval	() 95%; -0.15 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Body Mass Index (BMI)
Description	Estimated mean change from baseline in BMI after 26 weeks of treatment.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dietician	Control
Arm/Group Description	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.	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.
Measure Participants	306	305
Least Squares Mean (Standard Error) [kg/m^2]	-0.37 (0.08)	-0.20 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietician, Control
	Comments	Normal linear regression model with treatment, use of insulin secretagogue at screening, sex and region as factors, and age and BMI at baseline as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.137
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	0.17
	Confidence Interval	() 95%; -0.05 to 0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Glycosylated Haemoglobin (HbA1c)
Description	Estimated mean change from baseline in HbA1c after 26 weeks of treatment.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dietician	Control
Arm/Group Description	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.	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.
Measure Participants	306	305
Least Squares Mean (Standard Error) [percentage of glycosylated haemoglobin]	-0.93 (0.05)	-0.80 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietician, Control
	Comments	Normal linear regression model with treatment, strata, use of insulin secretagogue at screening and region as factors and HbA1c at baseline as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	0.13
	Confidence Interval	() 95%; -0.00 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG)
Description	Estimated mean change from baseline in FPG after 26 weeks of treatment.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dietician	Control
Arm/Group Description	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.	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.
Measure Participants	306	302
Least Squares Mean (Standard Error) [mmol/L]	-3.00 (0.12)	-2.93 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietician, Control
	Comments	Normal linear regression model with treatment, strata, use of insulin secretagogue at screening and region as factors and FPG at baseline as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.674
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	0.07
	Confidence Interval	() 95%; -0.25 to 0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Rate of Treatment Emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Week 0 to Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dietician	Control
Arm/Group Description	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.	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.
Measure Participants	305	301
All TEAEs	387.9	437.1
Serious TEAEs	16.3	16.6
Severe TEAEs	16.3	11.3
Moderate TEAEs	130.5	108.3
Mild TEAEs	241.0	317.5

6. Secondary Outcome

Title	Rate of All Treatment Emergent Hypoglycaemic Episodes
Description	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.
Time Frame	Week 0 to Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dietician	Control
Arm/Group Description	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.	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.
Measure Participants	305	301
All Events	25.47	23.30
Severe Events	0.01	0.01

7. Secondary Outcome

Title	Rate of Nocturnal Treatment Emergent Hypoglycaemic Episodes
Description	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.
Time Frame	Week 0 to Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dietician	Control
Arm/Group Description	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.	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.
Measure Participants	305	301
All Events	5.59	5.51
Severe Events	0.01	0.01

Adverse Events

Time Frame	The adverse events were collected in a time frame of 26 weeks.
Adverse Event Reporting Description	Safety analysis set includes all subjects who received at least one dose of insulin detemir.
Arm/Group Title	Dietician		Control
Arm/Group Description	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.		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.
All Cause Mortality
	Dietician		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dietician		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/305 (5.6%)		19/301 (6.3%)
Cardiac disorders
Acute coronary syndrome	1/305 (0.3%)	1	0/301 (0%)	0
Acute myocardial infarction	1/305 (0.3%)	1	2/301 (0.7%)	2
Angina pectoris	1/305 (0.3%)	1	0/301 (0%)	0
Cardiac disorder	1/305 (0.3%)	1	0/301 (0%)	0
Congestive cardiomyopathy	0/305 (0%)	0	1/301 (0.3%)	1
Myocardial infarction	1/305 (0.3%)	1	1/301 (0.3%)	1
Myocardial ischaemia	0/305 (0%)	0	1/301 (0.3%)	1
Tachycardia	0/305 (0%)	0	1/301 (0.3%)	1
Ear and labyrinth disorders
Vertigo positional	0/305 (0%)	0	1/301 (0.3%)	1
Eye disorders
Retinal vein thrombosis	0/305 (0%)	0	1/301 (0.3%)	1
Gastrointestinal disorders
Gastritis	0/305 (0%)	0	1/301 (0.3%)	1
General disorders
Chest pain	0/305 (0%)	0	1/301 (0.3%)	1
Infections and infestations
Anal abscess	1/305 (0.3%)	1	0/301 (0%)	0
Bronchitis	1/305 (0.3%)	1	1/301 (0.3%)	1
Bursitis infective	1/305 (0.3%)	1	0/301 (0%)	0
Lobar pneumonia	0/305 (0%)	0	1/301 (0.3%)	1
Pneumonia	1/305 (0.3%)	1	0/301 (0%)	0
Viral infection	1/305 (0.3%)	1	0/301 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/305 (0.3%)	1	0/301 (0%)	0
Wrist fracture	1/305 (0.3%)	1	0/301 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	1/305 (0.3%)	2	0/301 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	1/305 (0.3%)	1	0/301 (0%)	0
Metastases to central nervous system	1/305 (0.3%)	1	0/301 (0%)	0
Nervous system disorders
Lumbar radiculopathy	0/305 (0%)	0	1/301 (0.3%)	1
Migraine with aura	1/305 (0.3%)	1	0/301 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/305 (0%)	0	1/301 (0.3%)	1
Psychiatric disorders
Depression	0/305 (0%)	0	1/301 (0.3%)	1
Schizophrenia	1/305 (0.3%)	3	0/301 (0%)	0
Renal and urinary disorders
Calculus bladder	1/305 (0.3%)	1	0/301 (0%)	0
Calculus urinary	1/305 (0.3%)	1	1/301 (0.3%)	1
Nephrolithiasis	0/305 (0%)	0	1/301 (0.3%)	1
Obstructive uropathy	0/305 (0%)	0	1/301 (0.3%)	1
Reproductive system and breast disorders
Endometrial hypertrophy	0/305 (0%)	0	1/301 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/305 (0%)	0	2/301 (0.7%)	2
Vascular disorders
Hypertension	0/305 (0%)	0	1/301 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Dietician		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/305 (20%)		69/301 (22.9%)
General disorders
Injection site reaction	16/305 (5.2%)	21	13/301 (4.3%)	17
Infections and infestations
Nasopharyngitis	30/305 (9.8%)	39	38/301 (12.6%)	49
Nervous system disorders
Headache	23/305 (7.5%)	29	24/301 (8%)	36

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.