The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes

Sponsor

Novo Nordisk A/S (Industry)

Overall Status

Completed

CT.gov ID

NCT00856986

Collaborator

(none)

987

Enrollment

233

Locations

Arms

Duration (Months)

4.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial is conducted in Europe and North America. The aim of this clinical trial is to assess and compare the effect of insulin detemir in combination with liraglutide and metformin versus liraglutide and metformin in subjects with type 2 diabetes. Subjects will continue their own pre-trial metformin treatment during the trial.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Diabetes Mellitus, Type 2	Drug: liraglutide Drug: insulin detemir Drug: metformin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

987 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes. A 26 Week, Randomised, Open-label, Parallel-group, Multicentre, Multinational Trial With a 26 Week Extension

Study Start Date :

Mar 1, 2009

Actual Primary Completion Date :

Apr 1, 2010

Actual Study Completion Date :

Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lira 1.8 Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Drug: liraglutide Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection. Drug: metformin Metformin tablets, at least 1500 mg/day
Experimental: Insulin detemir + Lira 1.8 Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Drug: liraglutide Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection. Drug: insulin detemir Insulin detemir subcutaneous (under the skin) injection once daily. Dose will be titrated (individually adjusted) based on fasting self-measured plasma glucose levels according to a pre-specified algorithm Drug: metformin Metformin tablets, at least 1500 mg/day
Experimental: Non-Randomised Lira 1.8 Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Drug: liraglutide Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection. Drug: metformin Metformin tablets, at least 1500 mg/day
Other: Early Withdrawals Lira 1.8 Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Drug: liraglutide Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection. Drug: metformin Metformin tablets, at least 1500 mg/day
Other: Intensified group Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.	Drug: liraglutide Liraglutide 1.8 mg/day for subcutaneous (under the skin) injection. Drug: insulin detemir Insulin detemir subcutaneous (under the skin) injection once daily. Dose will be titrated (individually adjusted) based on fasting self-measured plasma glucose levels according to a pre-specified algorithm Drug: metformin Metformin tablets, at least 1500 mg/day

Outcome Measures

Primary Outcome Measures

Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 26. [Week 0 (Randomisation), week 26]

Secondary Outcome Measures

Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (for Intensified Subjects in Original Treatment Group) [Week 0, Week 52]
Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (Values Before Intensification as LOCF) [Week 0, Week 52]
Mean Change From Randomisation in Fasting Plasma Glucose at Week 26 [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Fasting Plasma Glucose at Week 52 [Week 0, Week 52]
Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 26 [Week 0 (Randomisation), Week 26]
Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline/randomisation (week 0) to 26 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.
Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 52 [Week 0, Week 52]
Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline (week 0) to 52 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.
Mean Change From Randomisation in Fasting Insulin at Week 26 [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Fasting Insulin at Week 52 [Week 0 (Randomisation), Week 52]
Mean Change From Randomisation in Fasting Pro-insulin at Week 26. [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Fasting Pro-insulin at Week 52 [Week 0, Week 52]
Mean Change From Randomisation in Fasting C-peptide at Week 26. [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Fasting C-peptide at Week 52. [Week 0, Week 52]
Mean Changes From Randomisation in Cholesterol Lipids at Week 26. [Week 0 (Randomisation), Week 26]
Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)
Mean Changes From Randomisation in Cholesterol Lipids at Week 52. [Week 0, Week 52]
Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)
Mean Change From Randomisation in Lipids: Triglycerides at Week 26 [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Lipids: Triglycerides at Week 52 [Week 0, Week 52]
Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 26 [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 52 [Week 0, Week 52]
Mean Change From Randomisation in Body Weight at Week 26 [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Body Weight at Week 52 [Week 0, Week 52]
Mean Change From Randomisation in Waist Circumference at Week 26. [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Waist Circumference at Week 52. [Week 0, Week 52]
Mean Change From Randomisation in Hip Circumference at Week 26 [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Hip Circumference at Week 52 [Week 0, week 52]
Mean Change From Randomisation in Waist to Hip Ratio at Week 26 [Week 0 (Randomisation), Week 26]
Waist to Hip Ratio is calculated by dividing Waist circumference with Hip circumference
Mean Change From Randomisation in Waist to Hip Ratio at Week 52 [Week 0, Week 52]
Waist to Hip Ratio is calculated by dividing Waist circumference with Hip circumference
Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 26. [Week 0 (Randomisation), Week 26]
Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 52. [Week 0, Week 52]
Adverse Events From Run-in (Week -12) to Week 52 [Run-in (week -12) to Week 52]
Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-26 [weeks 0-26]
Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Hypoglycaemic Episodes Weeks 0-52 [Week 0-52]
Number of hypoglycaemic episodes from Week 0 to Week 52, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 84 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects diagnosed with type 2 diabetes, insulin naïve and treated with metformin as monotherapy for at least 3 months prior to screening, at a stable dose of at least 1500 mg/day or metformin (at least 1500 mg/day) and a sulfonylurea (less than or equal to half of the maximum approved dose), both at a stable dose for at least 3 months prior to screening. Previous short-term insulin treatment in connection with intercurrent illness is allowed at the discretion of the Investigator
HbA1c 7.0-10.0% (both inclusive) for subjects on metformin monotherapy
HbA1c 7.0-8.5% (both inclusive) for subjects on metformin in combination with a sulphonylurea

Exclusion Criteria:

Previous treatment with insulin (except for short-term treatment in connection with intercurrent illness at the discretion of the Investigator)
Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria in a period of 3 months prior to screening
Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator
Impaired kidney function
Impaired liver function
Uncontrolled treated/untreated hypertension
Cancer or any clinically significant disease or disorder as judged by the Investigator
Previous participation in the run-in phase of this trial. Re-screening is allowed once
History of chronic pancreatitis or idiopathic pancreatitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Alexander City	Alabama	United States	35010
2	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35294
3	Novo Nordisk Investigational Site	Encino	California	United States	91436
4	Novo Nordisk Investigational Site	Fullerton	California	United States	92835
5	Novo Nordisk Investigational Site	Inglewood	California	United States	90301
6	Novo Nordisk Investigational Site	La Jolla	California	United States	92037
7	Novo Nordisk Investigational Site	Los Gatos	California	United States	95032
8	Novo Nordisk Investigational Site	Montclair	California	United States	91763
9	Novo Nordisk Investigational Site	Spring Valley	California	United States	91978
10	Novo Nordisk Investigational Site	Tustin	California	United States	92780
11	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
12	Novo Nordisk Investigational Site	Waterbury	Connecticut	United States	06712
13	Novo Nordisk Investigational Site	Bradenton	Florida	United States	34201
14	Novo Nordisk Investigational Site	Clearwater	Florida	United States	33765
15	Novo Nordisk Investigational Site	Jupiter	Florida	United States	33458-7200
16	Novo Nordisk Investigational Site	Miami	Florida	United States	33136
17	Novo Nordisk Investigational Site	Miami	Florida	United States	33156
18	Novo Nordisk Investigational Site	Miami	Florida	United States	33169
19	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30308-2253
20	Novo Nordisk Investigational Site	Decatur	Georgia	United States	30033
21	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
22	Novo Nordisk Investigational Site	Savannah	Georgia	United States	31405
23	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60616
24	Novo Nordisk Investigational Site	Quincy	Illinois	United States	62301
25	Novo Nordisk Investigational Site	Chicago Heights	Indiana	United States	60411
26	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
27	Novo Nordisk Investigational Site	Madisonville	Kentucky	United States	42431
28	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21204
29	Novo Nordisk Investigational Site	Hyattsville	Maryland	United States	20782
30	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
31	Novo Nordisk Investigational Site	Methuen	Massachusetts	United States	01844
32	Novo Nordisk Investigational Site	St. Louis	Missouri	United States	63104
33	Novo Nordisk Investigational Site	Bronx	New York	United States	10461-2665
34	Novo Nordisk Investigational Site	New Hyde Park	New York	United States	11042
35	Novo Nordisk Investigational Site	Northport	New York	United States	11768
36	Novo Nordisk Investigational Site	Syracuse	New York	United States	13210
37	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28277
38	Novo Nordisk Investigational Site	Durham	North Carolina	United States	27710
39	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45226
40	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45245
41	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45439
42	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73103
43	Novo Nordisk Investigational Site	Danville	Pennsylvania	United States	17822
44	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19152
45	Novo Nordisk Investigational Site	State College	Pennsylvania	United States	16801
46	Novo Nordisk Investigational Site	Willkes Barre	Pennsylvania	United States	18702
47	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37411
48	Novo Nordisk Investigational Site	Memphis	Tennessee	United States	38119
49	Novo Nordisk Investigational Site	Corpus Christi	Texas	United States	78412
50	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
51	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
52	Novo Nordisk Investigational Site	Dallas	Texas	United States	75235-6233
53	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
54	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
55	Novo Nordisk Investigational Site	Midland	Texas	United States	79707
56	Novo Nordisk Investigational Site	Plano	Texas	United States	75075
57	Novo Nordisk Investigational Site	Orem	Utah	United States	84058
58	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23249
59	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23294
60	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53209
61	Novo Nordisk Investigational Site	Bonheiden		Belgium	2820
62	Novo Nordisk Investigational Site	Leuven		Belgium	3000
63	Novo Nordisk Investigational Site	Edmonton	Alberta	Canada	T5J 3N4
64	Novo Nordisk Investigational Site	Winnipeg	Manitoba	Canada	R3E 3P4
65	Novo Nordisk Investigational Site	Halifax	Nova Scotia	Canada	B3H 2Y9
66	Novo Nordisk Investigational Site	London	Ontario	Canada	N6G 2M1
67	Novo Nordisk Investigational Site	Mississauga	Ontario	Canada	L5M 2V8
68	Novo Nordisk Investigational Site	Smiths Falls	Ontario	Canada	K7A 4W8
69	Novo Nordisk Investigational Site	Ajax		Canada	L1S 7K8
70	Novo Nordisk Investigational Site	Antibes		France	06600
71	Novo Nordisk Investigational Site	BRON cedex		France	69677
72	Novo Nordisk Investigational Site	CAHORS cedex 9		France	46005
73	Novo Nordisk Investigational Site	Corbeil Essonnes		France	91106
74	Novo Nordisk Investigational Site	Haguenau		France	67504
75	Novo Nordisk Investigational Site	LA ROCHELLE cedex		France	17019
76	Novo Nordisk Investigational Site	Le Creusot		France	71200
77	Novo Nordisk Investigational Site	MARSEILLE cedex 08		France	13285
78	Novo Nordisk Investigational Site	Marseille		France	13008
79	Novo Nordisk Investigational Site	MONTPELLIER cedex 5		France	34295
80	Novo Nordisk Investigational Site	Montpellier		France	34070
81	Novo Nordisk Investigational Site	Narbonne		France	11108
82	Novo Nordisk Investigational Site	Paris Cedex 10		France	75475
83	Novo Nordisk Investigational Site	Paris		France	75181
84	Novo Nordisk Investigational Site	PERPIGNAN cedex		France	66046
85	Novo Nordisk Investigational Site	Pessac		France	33600
86	Novo Nordisk Investigational Site	Poitiers		France	86000
87	Novo Nordisk Investigational Site	Reims		France	51056
88	Novo Nordisk Investigational Site	SAINT QUENTIN Cédex		France	02321
89	Novo Nordisk Investigational Site	Saint-denis de La Reunion		France	97405
90	Novo Nordisk Investigational Site	Saint-pierre de La Reunion		France	97448
91	Novo Nordisk Investigational Site	Strasbourg		France	67000
92	Novo Nordisk Investigational Site	Sète		France	34200
93	Novo Nordisk Investigational Site	Tours		France	37044
94	Novo Nordisk Investigational Site	Augsburg		Germany	86150
95	Novo Nordisk Investigational Site	Bad Kreuznach		Germany	55545
96	Novo Nordisk Investigational Site	Bad Mergentheim		Germany	97980
97	Novo Nordisk Investigational Site	Bad Nauheim		Germany	61231
98	Novo Nordisk Investigational Site	Berlin		Germany	10789
99	Novo Nordisk Investigational Site	Berlin		Germany	12163
100	Novo Nordisk Investigational Site	Berlin		Germany	13055
101	Novo Nordisk Investigational Site	Bremen		Germany	28213
102	Novo Nordisk Investigational Site	Dresden		Germany	01219
103	Novo Nordisk Investigational Site	Dresden		Germany	01307
104	Novo Nordisk Investigational Site	Duisburg		Germany	47051
105	Novo Nordisk Investigational Site	Eisenach		Germany	99817
106	Novo Nordisk Investigational Site	Erfurt		Germany	99085
107	Novo Nordisk Investigational Site	Esslingen		Germany	73728
108	Novo Nordisk Investigational Site	Frankfurt		Germany	60388
109	Novo Nordisk Investigational Site	Freiburg		Germany	79106
110	Novo Nordisk Investigational Site	Fulda		Germany	36037
111	Novo Nordisk Investigational Site	Gifhorn		Germany	38518
112	Novo Nordisk Investigational Site	Grevenbroich		Germany	41515
113	Novo Nordisk Investigational Site	Hamburg		Germany	21073
114	Novo Nordisk Investigational Site	Hamburg		Germany	22607
115	Novo Nordisk Investigational Site	Hohenmölsen		Germany	06679
116	Novo Nordisk Investigational Site	Jena		Germany	07743
117	Novo Nordisk Investigational Site	Leipzig		Germany	04103
118	Novo Nordisk Investigational Site	Leipzig		Germany	04275
119	Novo Nordisk Investigational Site	Limburg		Germany	65549
120	Novo Nordisk Investigational Site	Mainz-Ebersheim		Germany	55129
121	Novo Nordisk Investigational Site	Mainz		Germany	55131
122	Novo Nordisk Investigational Site	Mannheim		Germany	68163
123	Novo Nordisk Investigational Site	München		Germany	81925
124	Novo Nordisk Investigational Site	Münster		Germany	48145
125	Novo Nordisk Investigational Site	Neuwied		Germany	56564
126	Novo Nordisk Investigational Site	Rehlingen-Siersburg		Germany	66780
127	Novo Nordisk Investigational Site	Rosenheim		Germany	83022
128	Novo Nordisk Investigational Site	Schkeuditz		Germany	04435
129	Novo Nordisk Investigational Site	Sinsheim		Germany	74889
130	Novo Nordisk Investigational Site	St. Ingbert		Germany	66386
131	Novo Nordisk Investigational Site	Stuttgart		Germany	70184
132	Novo Nordisk Investigational Site	Wangen		Germany	88239
133	Novo Nordisk Investigational Site	Ancona		Italy	60100
134	Novo Nordisk Investigational Site	Caserta		Italy	81100
135	Novo Nordisk Investigational Site	Catanzaro Lido		Italy
136	Novo Nordisk Investigational Site	Catanzaro		Italy	88100
137	Novo Nordisk Investigational Site	Chiavari		Italy	16043
138	Novo Nordisk Investigational Site	Cosenza		Italy	87100
139	Novo Nordisk Investigational Site	Ferrara		Italy
140	Novo Nordisk Investigational Site	Lanciano		Italy
141	Novo Nordisk Investigational Site	Matera (mt)		Italy	75100
142	Novo Nordisk Investigational Site	Milano		Italy	20162
143	Novo Nordisk Investigational Site	Milano		Italy
144	Novo Nordisk Investigational Site	Monserrato, Cagliari		Italy	09042
145	Novo Nordisk Investigational Site	Monza		Italy	20052
146	Novo Nordisk Investigational Site	Palermo		Italy	90127
147	Novo Nordisk Investigational Site	Piacenza		Italy	29100
148	Novo Nordisk Investigational Site	Primo Piano Palazzina Ambulato		Italy	40133
149	Novo Nordisk Investigational Site	Ravenna		Italy	48121
150	Novo Nordisk Investigational Site	Reggio Calabria		Italy	89122
151	Novo Nordisk Investigational Site	Roma		Italy	00133
152	Novo Nordisk Investigational Site	Terni		Italy	05100
153	Novo Nordisk Investigational Site	Treviglio		Italy
154	Novo Nordisk Investigational Site	Amersfoort		Netherlands	3816 CP
155	Novo Nordisk Investigational Site	Amsterdam		Netherlands	1091 HA
156	Novo Nordisk Investigational Site	Amsterdam		Netherlands	1105 AZ
157	Novo Nordisk Investigational Site	Beek		Netherlands	6191JW
158	Novo Nordisk Investigational Site	Delft		Netherlands	2625 AD
159	Novo Nordisk Investigational Site	Doetinchem		Netherlands	7001 GW
160	Novo Nordisk Investigational Site	Eindhoven		Netherlands	5616 GB
161	Novo Nordisk Investigational Site	Groningen		Netherlands	9728 NT
162	Novo Nordisk Investigational Site	Heerlen		Netherlands	6419 PC
163	Novo Nordisk Investigational Site	Hoofddorp		Netherlands	2134 TM
164	Novo Nordisk Investigational Site	Hoogeveen		Netherlands	7909 AA
165	Novo Nordisk Investigational Site	Leiden		Netherlands	2334 CK
166	Novo Nordisk Investigational Site	Leiderdorp		Netherlands	2352 RA
167	Novo Nordisk Investigational Site	Lichtenvoorde		Netherlands	7131 CM
168	Novo Nordisk Investigational Site	Lieshout		Netherlands	5737 CB
169	Novo Nordisk Investigational Site	Oude Pekela		Netherlands	9665 AR
170	Novo Nordisk Investigational Site	Utrecht		Netherlands	3584 CX
171	Novo Nordisk Investigational Site	Voorburg		Netherlands	2275 CX
172	Novo Nordisk Investigational Site	Wildervank		Netherlands	9648 BE
173	Novo Nordisk Investigational Site	Winschoten		Netherlands	9671 CX
174	Novo Nordisk Investigational Site	Bayamon		Puerto Rico	00961
175	Novo Nordisk Investigational Site	Carolina		Puerto Rico	00983
176	Novo Nordisk Investigational Site	Trujillo Alto		Puerto Rico	00976
177	Novo Nordisk Investigational Site	Almería		Spain	04001
178	Novo Nordisk Investigational Site	Badajoz		Spain	06080
179	Novo Nordisk Investigational Site	Badalona		Spain	08916
180	Novo Nordisk Investigational Site	Bilbao		Spain	48013
181	Novo Nordisk Investigational Site	Cartagena		Spain	30203
182	Novo Nordisk Investigational Site	Cádiz		Spain	11009
183	Novo Nordisk Investigational Site	Córdoba		Spain	14004
184	Novo Nordisk Investigational Site	Girona		Spain	17007
185	Novo Nordisk Investigational Site	Granada		Spain	18012
186	Novo Nordisk Investigational Site	Madrid		Spain	28006
187	Novo Nordisk Investigational Site	Madrid		Spain	28031
188	Novo Nordisk Investigational Site	Madrid		Spain	28040
189	Novo Nordisk Investigational Site	Majadahonda		Spain	28222
190	Novo Nordisk Investigational Site	Pamplona		Spain	31008
191	Novo Nordisk Investigational Site	Pontevedra		Spain	36001
192	Novo Nordisk Investigational Site	Pozuelo de Alarcon		Spain	28223
193	Novo Nordisk Investigational Site	Salamanca		Spain	37007
194	Novo Nordisk Investigational Site	San Juan		Spain	03550
195	Novo Nordisk Investigational Site	San Sebastián de los Reyes		Spain	28700
196	Novo Nordisk Investigational Site	Santa Cruz de Tenerife		Spain	38010
197	Novo Nordisk Investigational Site	Sevilla		Spain	41013
198	Novo Nordisk Investigational Site	Tarrasa		Spain	08221
199	Novo Nordisk Investigational Site	Valencia		Spain	46010
200	Novo Nordisk Investigational Site	Xátiva		Spain	46800
201	Novo Nordisk Investigational Site	Zaragoza		Spain	50009
202	Novo Nordisk Investigational Site	Aberdeen		United Kingdom	AB25 1LD
203	Novo Nordisk Investigational Site	Ashton-Under-Lyne		United Kingdom	OL6 9RW
204	Novo Nordisk Investigational Site	Bath		United Kingdom	BA1 3NG
205	Novo Nordisk Investigational Site	Belfast		United Kingdom	BT12 6BA
206	Novo Nordisk Investigational Site	Belfast		United Kingdom	BT16 1RH
207	Novo Nordisk Investigational Site	Belfast		United Kingdom	BT41 2RL
208	Novo Nordisk Investigational Site	Blackburn		United Kingdom	BB2 3HH
209	Novo Nordisk Investigational Site	Bradford		United Kingdom	BD9 6RJ
210	Novo Nordisk Investigational Site	Bristol		United Kingdom	BS2 8HW
211	Novo Nordisk Investigational Site	Coventry		United Kingdom	CV2 2DX
212	Novo Nordisk Investigational Site	Derby		United Kingdom	DE22 3NE
213	Novo Nordisk Investigational Site	Dundee		United Kingdom	DD1 9SY
214	Novo Nordisk Investigational Site	Edgbaston, Birmingham		United Kingdom	B15 2TH
215	Novo Nordisk Investigational Site	Edinburgh		United Kingdom	EH4 2XU
216	Novo Nordisk Investigational Site	Exeter		United Kingdom	EX2 5AX
217	Novo Nordisk Investigational Site	Guildford		United Kingdom	GU2 7XX
218	Novo Nordisk Investigational Site	Hull		United Kingdom	HU3 2JZ
219	Novo Nordisk Investigational Site	Inverness		United Kingdom	IV2 3UJ
220	Novo Nordisk Investigational Site	Leicester		United Kingdom	LE1 5WW
221	Novo Nordisk Investigational Site	Liverpool		United Kingdom	L7 8XP
222	Novo Nordisk Investigational Site	Liverpool		United Kingdom	L9 7AL
223	Novo Nordisk Investigational Site	Londonderry		United Kingdom	BT47 6SB
224	Novo Nordisk Investigational Site	London		United Kingdom	E1 2EF
225	Novo Nordisk Investigational Site	Manchester		United Kingdom	M41 5SL
226	Novo Nordisk Investigational Site	Manchester		United Kingdom	M8 5RB
227	Novo Nordisk Investigational Site	Northampton		United Kingdom	NN1 5BD
228	Novo Nordisk Investigational Site	Nuneaton		United Kingdom	CV10 7DJ
229	Novo Nordisk Investigational Site	Oxford		United Kingdom	OX3 7LE
230	Novo Nordisk Investigational Site	Rugby		United Kingdom	CV22 5PX
231	Novo Nordisk Investigational Site	Salford		United Kingdom	M6 8HD
232	Novo Nordisk Investigational Site	Swansea		United Kingdom	SA6 6NL
233	Novo Nordisk Investigational Site	Welwyn Garden City		United Kingdom	AL7 4HQ

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Clinical Trials at Novo Nordisk

Publications

None provided.

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT00856986

Other Study ID Numbers:

NN2211-1842
2007-005317-19

First Posted:

Mar 6, 2009

Last Update Posted:

Mar 8, 2017

Last Verified:

Jan 1, 2017

Additional relevant MeSH terms:

Diabetes Mellitus

Diabetes Mellitus, Type 2

Metformin

Liraglutide

Insulin Detemir

Study Results

Participant Flow

Recruitment Details	A total of 202 centres in 9 countries: Belgium (2), Canada (7), France (19), Germany (37), Italy (18), the Netherlands (16), Spain (14), the United Kingdom (32) and the United States (57)
Pre-assignment Detail	Subjects on metformin and/or sulpholynurea treatment underwent a 12-week run-in period with liraglutide + metformin. Subjects not achieving an HbA1c below 7% were randomised to liraglutide + metformin treatment with/without insulin detemir. Subjects achieving an HbA1c below 7% continued liraglutide + metformin treatment.

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Period Title: Run-in Period, Weeks -12-0
STARTED	161	162	498	167	0
COMPLETED	161	162	498	0	0
NOT COMPLETED	0	0	0	167	0
Period Title: Run-in Period, Weeks -12-0
STARTED	161	162	498	0	0
COMPLETED	127	144	470	0	0
NOT COMPLETED	34	18	28	0	0
Period Title: Run-in Period, Weeks -12-0
STARTED	127	144	470	0	0
Enrolled in Extension	122	140	461	0	0
COMPLETED	108	130	432	0	0
NOT COMPLETED	19	14	38	0	0

Baseline Characteristics

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group	Total
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.	Total of all reporting groups
Overall Participants	161	162	498	166	24	1011
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.5 (9.8)	57 (9.5)	56.7 (9.7)	58.7 (10.8)	54.3 (10.3)	56.9 (9.7)
Sex: Female, Male (Count of Participants)
Female	72 44.7%	74 45.7%	216 43.4%	75 45.2%	11 45.8%	448 44.3%
Male	89 55.3%	88 54.3%	282 56.6%	91 54.8%	13 54.2%	563 55.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	25 15.5%	22 13.6%	48 9.6%	28 16.9%	5 20.8%	128 12.7%
Not Hispanic or Latino	136 84.5%	140 86.4%	450 90.4%	138 83.1%	19 79.2%	883 87.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.6%	0 0%	0 0%	0 0%	1 0.1%
Asian	1 0.6%	4 2.5%	5 1%	4 2.4%	0 0%	14 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.6%	0 0%	0 0%	0 0%	1 0.1%
Black or African American	17 10.6%	8 4.9%	19 3.8%	11 6.6%	1 4.2%	56 5.5%
White	141 87.6%	144 88.9%	470 94.4%	146 88%	22 91.7%	923 91.3%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.2%	4 2.5%	4 0.8%	5 3%	1 4.2%	16 1.6%
Height (meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meter]	1.7 (0.1)	1.69 (0.11)	1.7 (0.1)	1.68 (0.1)	1.72 (0.09)	1.69 (0.1)
Body weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	98.6 (21.3)	99.5 (21.2)	99 (20.8)	90.2 (18.5)	109 (25.7)	99 (21)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	33.9 (6)	34.9 (6.3)	34.4 (6.7)	31.8 (6)	36.5 (7.7)	34.4 (6.5)
Diabetes History (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.5 (6)	8.6 (5.8)	6.6 (5.7)	8.4 (6.4)	6.8 (5.4)	7.4 (5.8)
Glycosylated haemoglobin (HbA1c) (Percentage point of total HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage point of total HbA1c]	8.3 (0.8)	8.2 (0.7)	7.7 (0.7)	8 (0.8)	8.4 (0.7)	7.9 (0.8)
Fasting plasma glucose (FPG) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	10.3 (2.5)	10.2 (2.4)	9.2 (1.8)	9.5 (3)	10.4 (2.3)	9.6 (2.1)

Outcome Measures

1. Primary Outcome

Title	Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 26.
Description
Time Frame	Week 0 (Randomisation), week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	149	160	0	0	0
Least Squares Mean (Standard Error) [Percentage point of total HbA1c]	0.02 (0.07)	-0.51 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lira 1.8, Insulin Detemir + Lira 1.8
	Comments	The estimated treatment difference between Detemir+Lira 1.8 and Lira 1.8 as well as 95% confidence interval and p-value were calculated by an ANCOVA model with treatment, country and previous OAD as fixed factors and baseline value as covariate. The p-value reflects a two-sided test for the null hypothesis of no difference between the two treatment groups with a significance level of 5% and with the power of 90%.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Estimated Treatment Difference, LSMean
	Estimated Value	-0.52
	Confidence Interval	() 95% -0.68 to -0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (for Intensified Subjects in Original Treatment Group)
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	149	160	0	0	0
Least Squares Mean (Standard Error) [Percentage point of total HbA1c]	-0.1 (0.09)	-0.51 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lira 1.8, Insulin Detemir + Lira 1.8
	Comments	The estimated treatment difference between Detemir+Lira 1.8 and Lira 1.8 as well as 95% confidence interval and p-value were calculated by an ANCOVA model with treatment, country and previous OAD as fixed factors and baseline value as covariate. The p-value reflects a two-sided test for the null hypothesis of no difference between the two treatment groups with a significance level of 5%.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Estimated Treatment Difference, LSMean
	Estimated Value	-0.41
	Confidence Interval	() 95% -0.6 to -0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	The analysis values for intensified Lira 1.8 mg subjects were kept in the treatment group and the last observation carried forward (LOCF) method was applied.

3. Secondary Outcome

Title	Mean Change From Randomisation in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (Values Before Intensification as LOCF)
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) includes LOCF of last observation before intensification for randomised Lira 1.8 mg treatment group subjects who were intensified.

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	149	160	0	0	0
Least Squares Mean (Standard Error) [Percentage point of total HbA1c]	0.01 (0.09)	-0.5 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lira 1.8, Insulin Detemir + Lira 1.8
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Estimated treatment difference, LS mean
	Estimated Value	-0.51
	Confidence Interval	() 95% -0.7 to -0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	The mean change in HbA1c from randomisation to week 52 was analysed including the values before intensification as LOCF for intensified subjects

4. Secondary Outcome

Title	Mean Change From Randomisation in Fasting Plasma Glucose at Week 26
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	154	160	0	0	0
Least Squares Mean (Standard Error) [mmol/L]	-0.39 (0.19)	-2.12 (0.19)

5. Secondary Outcome

Title	Mean Change From Randomisation in Fasting Plasma Glucose at Week 52
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	154	160	0	0	0
Least Squares Mean (Standard Error) [mmol/L]	-0.14 (0.21)	-1.91 (0.21)

6. Secondary Outcome

Title	Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 26
Description	Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline/randomisation (week 0) to 26 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	133	144	0	0	0
Change at Breakfast, N=133, 144	-0.97 (0.26)	-2.09 (0.26)
Change at Lunch, N= 134, 143	-0.83 (0.22)	-1.43 (0.22)
Change at Dinner, N= 133, 139	-0.48 (0.24)	-1.18 (0.24)

7. Secondary Outcome

Title	Mean Change From Randomisation in 7-point Plasma Glucose Profile (Self-measured) at Week 52
Description	Calculated as an estimate of the change in mean prandial increment of plasma glucose after breakfast, lunch and dinner (from baseline (week 0) to 52 weeks), respectively. Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after each of these three meals, respectively.
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	136	148	0	0	0
Change at Breakfast, N=148, 135	-0.68 (0.25)	-2.43 (0.25)
Change at Lunch, N= 145, 136	-0.51 (0.25)	-1.14 (0.25)
Change at Dinner, N= 144, 135	-0.96 (0.26)	-1.4 (0.25)

8. Secondary Outcome

Title	Mean Change From Randomisation in Fasting Insulin at Week 26
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
Data on fasting insulin could not be obtained for the insulin detemir+liraglutide 1.8 mg+metformin (Detemir + Lira 1.8 group) treated subjects due to cross-reactivity between insulin detemir and the insulin assay. Data from both goups were therefore not further investigated by ANCOVA why no data is presented for this endpoint.

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	0	0	0	0	0

9. Secondary Outcome

Title	Mean Change From Randomisation in Fasting Insulin at Week 52
Description
Time Frame	Week 0 (Randomisation), Week 52

Outcome Measure Data

Analysis Population Description
Data on fasting insulin could not be obtained for the insulin detemir+liraglutide 1.8 mg+metformin (Detemir + Lira 1.8 group) treated subjects due to cross-reactivity between insulin detemir and the insulin assay. Data from both goups were therefore not further investigated by ANCOVA why no data is presented for this endpoint.

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	0	0	0	0	0

10. Secondary Outcome

Title	Mean Change From Randomisation in Fasting Pro-insulin at Week 26.
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	135	152	0	0	0
Least Squares Mean (Standard Error) [pmol/L]	-1.12 (3.27)	-9.78 (3.22)

11. Secondary Outcome

Title	Mean Change From Randomisation in Fasting Pro-insulin at Week 52
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	139	152	0	0	0
Least Squares Mean (Standard Error) [pmol/L]	1.47 (3.08)	-4 (3.08)

12. Secondary Outcome

Title	Mean Change From Randomisation in Fasting C-peptide at Week 26.
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	136	149	0	0	0
Least Squares Mean (Standard Error) [mmol/L]	-0.08 (0.04)	-0.32 (0.04)

13. Secondary Outcome

Title	Mean Change From Randomisation in Fasting C-peptide at Week 52.
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	139	150	0	0	0
Least Squares Mean (Standard Error) [mmol/L]	0.02 (0.05)	-0.34 (0.05)

14. Secondary Outcome

Title	Mean Changes From Randomisation in Cholesterol Lipids at Week 26.
Description	Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	141	152	0	0	0
Change in Total Cholesterol	0.04 (0.07)	0.05 (0.07)
Change in LDL-C	-0.04 (0.06)	-0.03 (0.06)
Change in VLDL-C	0.05 (0.03)	0.01 (0.03)
Change in HDL-C	0.02 (0.01)	0.05 (0.01)

15. Secondary Outcome

Title	Mean Changes From Randomisation in Cholesterol Lipids at Week 52.
Description	Cholesterol Lipids cover: Total Cholesterol, Low-density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), High Density Lipoprotein Cholesterol (HDL-C)
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	141	153	0	0	0
Change in Total Cholesterol	-0.02 (0.08)	-0.03 (0.08)
Change in LDL-C	-0.08 (0.07)	-0.1 (0.07)
Change in VLDL-C	0.03 (0.04)	-0.03 (0.04)
Change in HDL-C	0.02 (0.02)	0.07 (0.02)

16. Secondary Outcome

Title	Mean Change From Randomisation in Lipids: Triglycerides at Week 26
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	141	151	0	0	0
Least Squares Mean (Standard Error) [mmol/L]	-0.24 (0.11)	-0.33 (0.11)

17. Secondary Outcome

Title	Mean Change From Randomisation in Lipids: Triglycerides at Week 52
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	141	152	0	0	0
Least Squares Mean (Standard Error) [mmol/L]	-0.22 (0.11)	-0.37 (0.11)

18. Secondary Outcome

Title	Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 26
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	131	140	0	0	0
Least Squares Mean (Standard Error) [mmol/L]	-0.03 (0.02)	-0.11 (0.02)

19. Secondary Outcome

Title	Mean Change From Randomisation in Lipids: Free Fatty Acids (FFA) at Week 52
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	133	141	0	0	0
Least Squares Mean (Standard Error) [mmol/L]	-0.03 (0.03)	-0.07 (0.03)

20. Secondary Outcome

Title	Mean Change From Randomisation in Body Weight at Week 26
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	157	162	0	0	0
Least Squares Mean (Standard Error) [kg]	-0.95 (0.31)	-0.16 (0.31)

21. Secondary Outcome

Title	Mean Change From Randomisation in Body Weight at Week 52
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (last observation carried forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	157	162	0	0	0
Least Squares Mean (Standard Error) [kg]	-1.02 (0.41)	-0.05 (0.42)

22. Secondary Outcome

Title	Mean Change From Randomisation in Waist Circumference at Week 26.
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	148	160	0	0	0
Least Squares Mean (Standard Error) [cm]	-0.66 (0.46)	-0.78 (0.46)

23. Secondary Outcome

Title	Mean Change From Randomisation in Waist Circumference at Week 52.
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	148	160	0	0	0
Least Squares Mean (Standard Error) [participants]	-0.83 (0.54) -0.5%	-0.83 (0.53) -0.5%

24. Secondary Outcome

Title	Mean Change From Randomisation in Hip Circumference at Week 26
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	148	160	0	0	0
Least Squares Mean (Standard Error) [cm]	-0.36 (0.46)	-0.38 (0.45)

25. Secondary Outcome

Title	Mean Change From Randomisation in Hip Circumference at Week 52
Description
Time Frame	Week 0, week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	148	160	0	0	0
Least Squares Mean (Standard Error) [cm]	-0.79 (0.5)	-0.28 (0.49)

26. Secondary Outcome

Title	Mean Change From Randomisation in Waist to Hip Ratio at Week 26
Description	Waist to Hip Ratio is calculated by dividing Waist circumference with Hip circumference
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	148	160	0	0	0
Least Squares Mean (Standard Error) [cm/cm]	-0.00356 (0.004071)	-0.00332 (0.004032)

27. Secondary Outcome

Title	Mean Change From Randomisation in Waist to Hip Ratio at Week 52
Description	Waist to Hip Ratio is calculated by dividing Waist circumference with Hip circumference
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	148	160	0	0	0
Least Squares Mean (Standard Error) [cm/cm]	-0.00146 (0.004165)	-0.00438 (0.004126)

28. Secondary Outcome

Title	Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 26.
Description
Time Frame	Week 0 (Randomisation), Week 26

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	157	162	0	0	0
Systolic Blood Pressure	1.11 (1.22)	0.41 (1.23)
Diastolic Blood Pressure	-1.1 (0.77)	-0.4 (0.78)

29. Secondary Outcome

Title	Mean Change From Randomisation in Blood Pressure (Systolic and Diastolic) at Week 52.
Description
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description
The FAS (Full Analysis Set) using LOCF (Last Observation Carried Forward) is all randomised subjects with at least one of any efficacy value after the randomisation visit (baseline)

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	157	162	0	0	0
Systolic Blood Pressure	-0.74 (1.2)	0.16 (1.21)
Diastolic Blood Pressure	-0.66 (0.78)	0.11 (0.79)

30. Secondary Outcome

Title	Adverse Events From Run-in (Week -12) to Week 52
Description
Time Frame	Run-in (week -12) to Week 52

Outcome Measure Data

Analysis Population Description
The Safety Analysis Set included all exposed subjects

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	159	163	499	166	24
Number [events]	716	845	2389	383	30

31. Secondary Outcome

Title	Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-26
Description	Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Time Frame	weeks 0-26

Outcome Measure Data

Analysis Population Description
The Safety Analysis Set included all exposed subjects. An outlier subject from the lira 1.8 group, who experienced an extreme number of minor and symptoms only hypoglycaemic episodes was excluded from this analysis.

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	158	163	499	0	0
Major	0	0	0
Minor	2	22	31
Symptoms only	9	19	26

32. Secondary Outcome

Title	Hypoglycaemic Episodes Weeks 0-52
Description	Number of hypoglycaemic episodes from Week 0 to Week 52, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Time Frame	Week 0-52

Outcome Measure Data

Analysis Population Description
The Safety Analysis Set included all exposed subjects. An outlier subject from the lira 1.8 group, who experienced an extreme number of minor and symptoms only hypoglycaemic episodes was excluded from this analysis

Arm/Group Title	Lira 1.8	Insulin Detemir + Lira 1.8	Non-Randomised Lira 1.8	Early Withdrawals Lira 1.8	Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial	Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
Measure Participants	159	163	499	0	24
Major	0	0	0	0
Minor	4	33	53	1
Symptoms only	14	57	42	2
Unknown	0	1	2	0

Adverse Events

	Lira 1.8		Insulin Detemir + Lira 1.8		Non-Randomised Lira 1.8		Early Withdrawals Lira 1.8		Intensified Group
Time Frame	The adverse events were collected in a timeframe of 64 weeks (from run-in to week 52).
Adverse Event Reporting Description	The Safety Analysis Set included all exposed subjects

Arm/Group Title	Lira 1.8		Insulin Detemir + Lira 1.8		Non-Randomised Lira 1.8		Early Withdrawals Lira 1.8		Intensified Group
Arm/Group Description	Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%		Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects were randomised to continue to receive liraglutide 1.8 mg once daily + metformin in addition to individually adjusted insulin detemir for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was at least 7.0%		Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Subjects continued to receive liraglutide 1.8 mg once daily + metformin for 26 weeks plus 26 weeks extension, when the HbA1c assessment after run-in period was below 7.0%		Subcutaneous administration of liraglutide 1.8 mg once daily in a forced 12 week run-in period + subject's own pre-trial metformin treatment at an unchanged dose and frequency (at least 1500 mg daily). Initial dose of liraglutide 0.6 mg/day with weekly increments of 0.6 mg until final dose of 1.8 mg/day was reached. Due to withdrawals in the run-in period, subjects did not receive any further treatment in trial		Intensification of treatment with insulin detemir was offered at Weeks 26 and 38 for subjects with an HbA1c ≥ 8.0% in the randomised Lira 1.8 group and non-randomised liraglutide treatment group.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lira 1.8		Insulin Detemir + Lira 1.8		Non-Randomised Lira 1.8		Early Withdrawals Lira 1.8		Intensified Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/159 (6.9%)		17/163 (10.4%)		62/499 (12.4%)		6/166 (3.6%)		1/24 (4.2%)
Blood and lymphatic system disorders
Febrile neutropenia	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Thrombocytopenic purpura	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Cardiac disorders
Angina Pectoris	1/159 (0.6%)	1	1/163 (0.6%)	1	1/499 (0.2%)	1	1/166 (0.6%)	1	0/24 (0%)	0
Coronary Artery Disease	0/159 (0%)	0	1/163 (0.6%)	1	4/499 (0.8%)	4	0/166 (0%)	0	0/24 (0%)	0
Supraventricular Tachycardia	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	5	0/166 (0%)	0	0/24 (0%)	0
Cardiac failure	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Tachycardia	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Ear and labyrinth disorders
Vertigo Positional	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Endocrine disorders
Goitre	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Thyroid ccell hyperplasia	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Eye disorders
Macular Ischaemia	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Macular Oedema	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Gastrointestinal disorders
Abdominal Pain	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Abdominal Hernia Obstructive	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Intestinal Infarction	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Pancreatitis Chronic	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Food Poisoning	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Abdominal pain upper	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Anal fistula	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Pancreatitis acute	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	1/166 (0.6%)	1	0/24 (0%)	0
General disorders
Chest Pain	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Immune system disorders
Sarcoidosis	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Infections and infestations
Clostridium Difficile Colitis	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Helicobacter Gastritis	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Post Procedural Infection	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Viral Infection	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Cellulitis	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Diverticulitis	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Injection site abscess	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Muscle abscess	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Pneumonia	0/159 (0%)	0	0/163 (0%)	0	2/499 (0.4%)	2	0/166 (0%)	0	0/24 (0%)	0
Injury, poisoning and procedural complications
Ankle Fracture	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Head Injury	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Joint Injury	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Fall	0/159 (0%)	0	0/163 (0%)	0	2/499 (0.4%)	2	0/166 (0%)	0	0/24 (0%)	0
Femur Fracture	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Ligament Rupture	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Traumatic Fracture	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Traumatic Intracranial Haemorrhage	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Tendon Rupture	0/159 (0%)	0	1/163 (0.6%)	1	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Post Lumbar Puncture Syndrome	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Rib Fracture	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Thermal burn	0/159 (0%)	0	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	1/24 (4.2%)	1
Upper Limb Fracture	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Investigations
ECG abnormal	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
ECG change	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	0/159 (0%)	0	0/163 (0%)	0	0/499 (0%)	0	1/166 (0.6%)	1	0/24 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/159 (0.6%)	1	1/163 (0.6%)	1	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Arthritis	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Bursitis	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Interverterbal Disc Degeneration	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	2	0/166 (0%)	0	0/24 (0%)	0
Interverterbal Disc Protrusion	0/159 (0%)	0	0/163 (0%)	0	2/499 (0.4%)	2	0/166 (0%)	0	0/24 (0%)	0
Polymyalgia Rheumatica	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Myalgia	0/159 (0%)	0	0/163 (0%)	0	0/499 (0%)	0	1/166 (0.6%)	1	0/24 (0%)	0
Periarthritis	0/159 (0%)	0	0/163 (0%)	0	2/499 (0.4%)	2	0/166 (0%)	0	0/24 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Metastases to Central Nervous System	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Renal Cancer	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Thyroid Cancer	0/159 (0%)	0	0/163 (0%)	0	0/499 (0%)	0	1/166 (0.6%)	1	0/24 (0%)	0
Uterine Leiomyoma	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Lung Squamous Cell Carcinoma Unspecified	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
B-Cell Lymphoma	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Fibroadenoma of Breast	0/0 (NaN)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Gallbladder Cancer	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Gastric Cancer	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Metastases to liver	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Prostate Cancer	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Nervous system disorders
Convulsion	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Benign Intracranial Hypertension	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Cerebrovascular Accident	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Syncope	0/159 (0%)	0	0/163 (0%)	0	2/499 (0.4%)	2	0/166 (0%)	0	0/24 (0%)	0
Transient Ischaemic Attack	0/159 (0%)	0	0/163 (0%)	0	2/499 (0.4%)	2	0/166 (0%)	0	0/24 (0%)	0
Carotid Artery Stenosis	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Partial Seizures	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Psychiatric disorders
Depression	0/159 (0%)	0	2/163 (1.2%)	2	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Anxiety	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/159 (0%)	0	1/163 (0.6%)	1	1/499 (0.2%)	1	1/166 (0.6%)	1	0/24 (0%)	0
Urinary Retention	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Renal Colic	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Renal Failure	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Renal failure acute	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Reproductive system and breast disorders
Cystocele	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Benign prostatic hyperplasia	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Breast hyperplasia	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Erectile Dysfunction	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Fibrocystic Breast Disease	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Vaginal Haemorrhage	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary Disease	0/159 (0%)	0	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Nasal Septum Deviation	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Epistaxis	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Pulmonary Mass	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Skin and subcutaneous tissue disorders
Eczema	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Skin ulcer	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	1	0/166 (0%)	0	0/24 (0%)	0
Surgical and medical procedures
Medical device removal	1/159 (0.6%)	1	0/163 (0%)	0	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Vascular disorders
Peripheral Arterial Occlusive Disease	1/159 (0.6%)	1	1/163 (0.6%)	1	0/499 (0%)	0	0/166 (0%)	0	0/24 (0%)	0
Poor Peripheral Circulation	0/159 (0%)	0	0/163 (0%)	0	1/499 (0.2%)	2	0/166 (0%)	0	0/24 (0%)	0
Other (Not Including Serious) Adverse Events
	Lira 1.8		Insulin Detemir + Lira 1.8		Non-Randomised Lira 1.8		Early Withdrawals Lira 1.8		Intensified Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	100/159 (62.9%)		102/163 (62.6%)		310/499 (62.1%)		122/166 (73.5%)		11/24 (45.8%)
Gastrointestinal disorders
Diarrhoea	26/159 (16.4%)	29	29/163 (17.8%)	42	74/499 (14.8%)	108	21/166 (12.7%)	25	1/24 (4.2%)	1
Nausea	37/159 (23.3%)	51	30/163 (18.4%)	40	136/499 (27.3%)	204	66/166 (39.8%)	72	1/24 (4.2%)	1
Vomiting	19/159 (11.9%)	21	17/163 (10.4%)	26	50/499 (10%)	113	21/166 (12.7%)	25	0/24 (0%)	0
Dyspepsia	8/159 (5%)	11	10/163 (6.1%)	11	42/499 (8.4%)	54	33/166 (19.9%)	42	0/24 (0%)	0
Constipation	11/159 (6.9%)	11	8/163 (4.9%)	10	25/499 (5%)	30	11/166 (6.6%)	11	0/24 (0%)	0
Abdominal Pain	8/159 (5%)	11	6/163 (3.7%)	7	14/499 (2.8%)	17	5/166 (3%)	6	0/24 (0%)	0
General disorders
Fatigue	9/159 (5.7%)	10	12/163 (7.4%)	13	15/499 (3%)	16	6/166 (3.6%)	8	0/24 (0%)	0
Infections and infestations
Nasopharyngitis	40/159 (25.2%)	57	33/163 (20.2%)	45	72/499 (14.4%)	97	2/166 (1.2%)	2	3/24 (12.5%)	3
Upper respiratory tract infection	9/159 (5.7%)	14	13/163 (8%)	13	21/499 (4.2%)	24	0/166 (0%)	0	0/24 (0%)	0
Investigations
Lipase Increased	16/159 (10.1%)	17	26/163 (16%)	27	55/499 (11%)	60	6/166 (3.6%)	7	4/24 (16.7%)	4
Metabolism and nutrition disorders
Decreased Appetite	9/159 (5.7%)	9	13/163 (8%)	13	50/499 (10%)	53	17/166 (10.2%)	17	0/24 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	10/159 (6.3%)	10	4/163 (2.5%)	6	26/499 (5.2%)	30	4/166 (2.4%)	5	1/24 (4.2%)	1
Nervous system disorders
Headache	23/159 (14.5%)	41	21/163 (12.9%)	54	73/499 (14.6%)	144	13/166 (7.8%)	22	2/24 (8.3%)	2
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain	10/159 (6.3%)	11	5/163 (3.1%)	5	17/499 (3.4%)	19	2/166 (1.2%)	2	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

Novo Nordisk reserves the right not to release data until specified milestones, e.g. a clinical trial report is available. This includes the right not to release interim results from clinical trials. At the end of the trial, one or more manuscripts for publication will be prepared in collaboration between Investigator(s) and Novo Nordisk. Novo Nordisk will not suppress or veto publications. Novo Nordisk reserves the right to postpone publication for a short time to protect intellectual property.

Results Point of Contact

Name/Title	Public Access to Clinical Trials
Organization	Novo Nordisk A/S
Phone
Email	clinicaltrials@novonordisk.com

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT00856986

Other Study ID Numbers:

NN2211-1842
2007-005317-19

First Posted:

Mar 6, 2009

Last Update Posted:

Mar 8, 2017

Last Verified:

Jan 1, 2017

The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes

Study Details

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Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

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