DUAL™IV: The Efficacy of Insulin Degludec/Liraglutide as add-on Therapy in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on Sulphonylurea With or Without Metformin Therapy

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01618162
• Collaborator: (none)
• Enrollment: 435
• Locations: 87
• Arms: 2
• Actual Duration (Months): 13.8
• Patients Per Site: 5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This trial is conducted in Asia, Europe and the United States of America (USA). The aim of this trial is to investigate the efficacy and safety of insulin degludec/liraglutide in insulin naïve subjects inadequately controlled with SU (sulphonylurea) alone or in combination with metformin. All subjects will continue their pre-trial SU treatment with or without metformin treatment without changing the frequency or dose throughout the trial.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: insulin degludec/liraglutide; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 435 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Efficacy of Insulin Degludec/Liraglutide as add-on Therapy in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on Sulphonylurea With or Without Metformin Therapy
• Actual Study Start Date: Aug 29, 2012
• Actual Primary Completion Date: Oct 23, 2013
• Actual Study Completion Date: Oct 23, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin degludec/liraglutide	Drug: insulin degludec/liraglutide; Injected subcutaneously (under the skin) once daily. Dose individually adjusted.
Placebo Comparator: Placebo	Drug: placebo; Injected subcutaneously (under the skin) once daily.

Outcome Measures

Primary Outcome Measures

1. Change in Glycosylated Haemoglobin (HbA1c) [Week 0, Week 26]

   Change in HbA1c from baseline to 26 weeks.

Secondary Outcome Measures

1. Responders Achieving Pre-defined Target: HbA1c Below 7.0% (53 mmol/Mol) [Week 26]

   Percentage of subjects having HbA1c below 7% at week 26.

2. Responders Achieving Pre-defined Target: HbA1c Below or Equal to 6.5% (48 mmol/Mol) [Week 26]

   Percentage of subjects having HbA1c below 6.5% at week 26

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

   Change from baseline in FPG at week 26.

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

   Change from baseline in body weight at week 26.

5. Number of Treatment Emergent (Confirmed) Hypoglycaemic Episodes [After 26 weeks of treatment]

   An event was treatment emergent if the onset of the episode occurs after the first administration of trial product and no later than 7 days after last trial product administration. Confirmed hypoglycaemic episodes were defined as hypoglycaemic episodes that were either severe or minor. Minor hypoglycaemic episodes were defined as: An episode with symptoms consistent with hypoglycaemia and confirmed by blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL) and which was handled by the subject himself/herself. Any asymptomatic PG value <3.1 mmol/L (56 mg/dL) or blood glucose value <2.8 mmol/L (50 mg/dL). Severe hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Reported values are hypoglycemia event rate per 100 patient-years of exposure (PYE).

6. Number of Adverse Events (AEs) [After 26 weeks of treatment]

   An AE was any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. Reported values are hypoglycemia event rate per 100 PYE.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects with type 2 diabetes mellitus

• HbA1c 7.0-9.0% (53-75 mmol/mol) (both inclusive)

• Subjects on stable daily dose of sulphonylurea (above or equal to half of the max approved dose according to local label) with or without metformin (above or equal to 1500 mg or max tolerated dose) for at least 90 days prior to screening visit (Visit 1)

• Body Mass Index (BMI) below or equal to 40 kg/m^2

Exclusion Criteria:

• Any use of oral anti-diabetic drugs (OADs) (other than SU in monotherapy or in combinationwith metformin) below or equal to 90 days prior to screening visit (Visit

• Use of any drug (other than SU in monotherapy or in combination with metformin), which in the Investigators opinion could interfere with the blood glucose level (e.g. systemic corticosteroids)

• Previous treatment with glucagon-like peptide-1 (GLP-1) receptor agonist (e.g. exenatide, liraglutide)

• Treatment with any insulin regimen (short term treatment due to intercurrent illness including gestational diabetes is allowed at the discretion of the Investigator)

• Screening calcitonin above or equal to 50 ng/l

• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)

• Cardiovascular disorders defined as: congestive heart failure (New York Heart Association (NYHA) class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the past 52 weeks prior to screening visit (Visit 1) and/or planned coronary,carotid or peripheral artery revascularisation procedures

• Proliferative retinopathy requiring acute treatment or maculopathy (macular oedema) according to the Investigator's opinion

• Subjects with a clinical significant, active (during the past 12 months) disease of the gastrointestinal, pulmonary, endocrinological (except for the Type 2 Diabetes Mellitus),neurological, genitourinary or haematological system that in the opinion of the Investigator,may confound the results of the trial or pose additional risk in administering trial product

• History of chronic pancreatitis or idiopathic acute pancreatitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Anaheim	California	United States	92801
2	Novo Nordisk Investigational Site	Garden Grove	California	United States	92844
3	Novo Nordisk Investigational Site	La Jolla	California	United States	92037
4	Novo Nordisk Investigational Site	Long Beach	California	United States	90807
5	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
6	Novo Nordisk Investigational Site	San Mateo	California	United States	94401
7	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
8	Novo Nordisk Investigational Site	Kissimmee	Florida	United States	34741
9	Novo Nordisk Investigational Site	Melbourne	Florida	United States	32934
10	Novo Nordisk Investigational Site	Miami	Florida	United States	33136
11	Novo Nordisk Investigational Site	Miami	Florida	United States	33156
12	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30318
13	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
14	Novo Nordisk Investigational Site	Meridian	Idaho	United States	83646
15	Novo Nordisk Investigational Site	Gurnee	Illinois	United States	60031
16	Novo Nordisk Investigational Site	Crestview Hills	Kentucky	United States	41017-3464
17	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
18	Novo Nordisk Investigational Site	Troy	Michigan	United States	48098
19	Novo Nordisk Investigational Site	Chesterfield	Missouri	United States	63017
20	Novo Nordisk Investigational Site	Saint Charles	Missouri	United States	63303
21	Novo Nordisk Investigational Site	Nashua	New Hampshire	United States	03063
22	Novo Nordisk Investigational Site	Lodi	New Jersey	United States	076444
23	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
24	Novo Nordisk Investigational Site	Tabor City	North Carolina	United States	28463
25	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45220-2213
26	Novo Nordisk Investigational Site	Franklin	Ohio	United States	45005
27	Novo Nordisk Investigational Site	Mason	Ohio	United States	45040-6815
28	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73104-5020
29	Novo Nordisk Investigational Site	Beaver	Pennsylvania	United States	15009
30	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19152
31	Novo Nordisk Investigational Site	Greer	South Carolina	United States	29651
32	Novo Nordisk Investigational Site	Pelzer	South Carolina	United States	29669
33	Novo Nordisk Investigational Site	Simpsonville	South Carolina	United States	29681
34	Novo Nordisk Investigational Site	Spartanburg	South Carolina	United States	29303
35	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
36	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
37	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37203
38	Novo Nordisk Investigational Site	Dallas	Texas	United States	75203
39	Novo Nordisk Investigational Site	Dallas	Texas	United States	75251
40	Novo Nordisk Investigational Site	Hurst	Texas	United States	76054
41	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77478
42	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84107
43	Novo Nordisk Investigational Site	Newport News	Virginia	United States	23606
44	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23219
45	Novo Nordisk Investigational Site	Lukovit		Bulgaria	5770
46	Novo Nordisk Investigational Site	Ruse		Bulgaria	7000
47	Novo Nordisk Investigational Site	Sofia		Bulgaria	1324
48	Novo Nordisk Investigational Site	Sofia		Bulgaria	1431
49	Novo Nordisk Investigational Site	Sofia		Bulgaria	1606
50	Novo Nordisk Investigational Site	Burnaby	British Columbia	Canada	V5G 1T4
51	Novo Nordisk Investigational Site	Surrey	British Columbia	Canada	V3S 2N6
52	Novo Nordisk Investigational Site	Victoria	British Columbia	Canada	V8V 3N7
53	Novo Nordisk Investigational Site	Cambridge	Ontario	Canada	N1R 7L6
54	Novo Nordisk Investigational Site	London	Ontario	Canada	N6G 2M1
55	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M4S 1Y2
56	Novo Nordisk Investigational Site	Mirabel	Quebec	Canada	J7J 2K8
57	Novo Nordisk Investigational Site	Pointe Claire	Quebec	Canada	H9R 4S3
58	Novo Nordisk Investigational Site	Sherbrooke	Quebec	Canada	J1G 5K2
59	Novo Nordisk Investigational Site	Quebec		Canada	G1N 4V3
60	Novo Nordisk Investigational Site	Esslingen		Germany	73728
61	Novo Nordisk Investigational Site	Hamburg		Germany	22607
62	Novo Nordisk Investigational Site	Hohenmölsen		Germany	06679
63	Novo Nordisk Investigational Site	Münster		Germany	48145
64	Novo Nordisk Investigational Site	Pohlheim		Germany	35415
65	Novo Nordisk Investigational Site	Rehlingen-Siersburg		Germany	66780
66	Novo Nordisk Investigational Site	Sulzbach-Rosenberg		Germany	92237
67	Novo Nordisk Investigational Site	Guwahati	Assam	India	781007
68	Novo Nordisk Investigational Site	Guwahati	Assam	India
69	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560043
70	Novo Nordisk Investigational Site	Belgaum	Karnataka	India	590001
71	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400008
72	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411030
73	Novo Nordisk Investigational Site	Delhi	New Delhi	India	110002
74	Novo Nordisk Investigational Site	Hyderabad		India	600034
75	Novo Nordisk Investigational Site	Haifa		Israel	35152
76	Novo Nordisk Investigational Site	Holon		Israel	58100
77	Novo Nordisk Investigational Site	Jerusalem		Israel	91120
78	Novo Nordisk Investigational Site	Kfar Saba		Israel	44281
79	Novo Nordisk Investigational Site	Petah-Tikva		Israel	49100
80	Novo Nordisk Investigational Site	Tel Hashomer		Israel	52621
81	Novo Nordisk Investigational Site	Tel-Aviv		Israel	64239
82	Novo Nordisk Investigational Site	Manati		Puerto Rico	00674
83	Novo Nordisk Investigational Site	Ankara		Turkey	06110
84	Novo Nordisk Investigational Site	Antalya		Turkey	07058
85	Novo Nordisk Investigational Site	Gaziantep		Turkey	27070
86	Novo Nordisk Investigational Site	Istanbul		Turkey	34752
87	Novo Nordisk Investigational Site	Izmir		Turkey	35100

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

• Khunti K, Mohan V, Jain SM, Boesgaard TW, Begtrup K, Sethi B. Efficacy and Safety of IDegLira in Participants with Type 2 Diabetes in India Uncontrolled on Oral Antidiabetic Drugs and Basal Insulin: Data from the DUAL Clinical Trial Program. Diabetes Ther. 2017 Jun;8(3):673-682. doi: 10.1007/s13300-017-0252-9. Epub 2017 Mar 22.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01618162
• Other Study ID Numbers: NN9068-3951; 2012-000140-97; U1111-1126-9776
• First Posted: Jun 13, 2012
• Last Update Posted: Oct 27, 2017
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Liraglutide; Xultophy

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 77 sites in 7 countries: Bulgaria (7), Canada (9), Germany (6), India (6), Israel (7), Turkey (3), United States (39).
Pre-assignment Detail	The trial included a 2 week screening period to assess subject eligibility.

Arm/Group Title	IDegLira	Placebo
Arm/Group Description	In this arm, subjects suboptimally controlled on sulfonyl urea (SU) +/- metformin, were given subcutenaous (s.c.) injection of insulin degludec/liraglutide (IDegLira). SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).
Period Title: Overall Study
STARTED	289	146
Exposed	288	146
COMPLETED	251	111
NOT COMPLETED	38	35

Baseline Characteristics

Arm/Group Title	IDegLira	Placebo	Total
Arm/Group Description	In this arm, Subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	Total of all reporting groups
Overall Participants	289	146	435
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (9.6)	59.4 (10.8)	59.8 (10.0)
Sex: Female, Male (Count of Participants)
Female	135 46.7%	73 50%	208 47.8%
Male	154 53.3%	73 50%	227 52.2%
Glycosylated haemoglobin (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	7.9 (0.6)	7.9 (0.6)	7.9 (0.6)
Fasting plasma glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	9.1 (2.2)	9.1 (2.1)	9.1 (2.1)
Body weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	87.2 (18.6)	89.3 (17.5)	87.9 (18.2)

Outcome Measures

1. Primary Outcome

Title	Change in Glycosylated Haemoglobin (HbA1c)
Description	Change in HbA1c from baseline to 26 weeks.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

Full analysis set.

Arm/Group Title	IDegLira	Placebo
Arm/Group Description	In this arm, Subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).
Measure Participants	289	146
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-1.45 (0.84)	-0.46 (0.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IDegLira, Placebo
	Comments	Superiority of IDegLira versus placebo therapy would be concluded if the 95% CI for the treatment differences for change in HbA1c lied entirely below 0%; implying that the two-sided p-value calculated by the ANCOVA model for testing the hypothesis of no difference between treatments was less than 5%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -1.18 to -0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Responders Achieving Pre-defined Target: HbA1c Below 7.0% (53 mmol/Mol)
Description	Percentage of subjects having HbA1c below 7% at week 26.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Full analysis set.

Arm/Group Title	IDegLira	Placebo
Arm/Group Description	In this arm, Subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).
Measure Participants	289	146
Number [percentage of subjects]	79.2	28.8

3. Secondary Outcome

Title	Responders Achieving Pre-defined Target: HbA1c Below or Equal to 6.5% (48 mmol/Mol)
Description	Percentage of subjects having HbA1c below 6.5% at week 26
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Full analysis set.

Arm/Group Title	IDegLira	Placebo
Arm/Group Description	In this arm, Subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).
Measure Participants	289	146
Number [percentage of subjects]	64	12.3

4. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG)
Description	Change from baseline in FPG at week 26.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

Full analysis set. Number of subjects analyzed=subjects with data available for FPG.

Arm/Group Title	IDegLira	Placebo
Arm/Group Description	In this arm, Subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).
Measure Participants	286	144
Mean (Standard Deviation) [mmol/L]	-2.6 (2.61)	-0.31 (2.43)

5. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	Change from baseline in body weight at week 26.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

Full analysis set.

Arm/Group Title	IDegLira	Placebo
Arm/Group Description	In this arm, Subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).
Measure Participants	289	146
Mean (Standard Deviation) [kilogram]	0.5 (3.1)	-1 (2.6)

6. Secondary Outcome

Title	Number of Treatment Emergent (Confirmed) Hypoglycaemic Episodes
Description	An event was treatment emergent if the onset of the episode occurs after the first administration of trial product and no later than 7 days after last trial product administration. Confirmed hypoglycaemic episodes were defined as hypoglycaemic episodes that were either severe or minor. Minor hypoglycaemic episodes were defined as: An episode with symptoms consistent with hypoglycaemia and confirmed by blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL) and which was handled by the subject himself/herself. Any asymptomatic PG value <3.1 mmol/L (56 mg/dL) or blood glucose value <2.8 mmol/L (50 mg/dL). Severe hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Reported values are hypoglycemia event rate per 100 patient-years of exposure (PYE).
Time Frame	After 26 weeks of treatment

Outcome Measure Data

Analysis Population Description

Safety analysis set included all subjects receiving at least one dose of the trial product.

Arm/Group Title	IDegLira	Placebo
Arm/Group Description	In this arm, Subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).
Measure Participants	288	146
Number [event rate per 100 PYE]	351.7	135.2

7. Secondary Outcome

Title	Number of Adverse Events (AEs)
Description	An AE was any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. Reported values are hypoglycemia event rate per 100 PYE.
Time Frame	After 26 weeks of treatment

Outcome Measure Data

Analysis Population Description

Safety analysis set.

Arm/Group Title	IDegLira	Placebo
Arm/Group Description	In this arm, Subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).	In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).
Measure Participants	288	146
Number [event rate per 100 PYE]	401.4	367

Adverse Events

Time Frame	After 26 weeks of treatment
Adverse Event Reporting Description	Safety analysis set included 434 subjects (288 in IDegLira and 146 in placebo).
Arm/Group Title	IDegLira		Placebo
Arm/Group Description	In this arm, Subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. IDegLira was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Treatment with IDegLira was initiated at 10 dose steps containing 10 units insulin degludec and 0.36 mg liraglutide. Adjustment of the IDegLira dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).		In this arm, subjects suboptimally controlled on SU +/- metformin, were given s.c. injection of placebo solution (matched to IDegLira) and was initiated and titrated as described for IDegLira. SU and metformin were maintained at the stable pre-trial dose throughout the duration of the trial. Placebo solution was injected in the thigh, upper arm (deltoid region) or abdomen once daily preferably at the same time every day. The injection area chosen remained unchanged throughout the trial, but rotation within the area was recommended. Adjustment of placebo was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-6.0 mmol/L).
All Cause Mortality
	IDegLira		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IDegLira		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/288 (4.9%)		5/146 (3.4%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/288 (0.3%)	1	0/146 (0%)	0
Cardiac disorders
Acute myocardial infarction	1/288 (0.3%)	1	0/146 (0%)	0
Arrhythmia	1/288 (0.3%)	1	0/146 (0%)	0
Atrioventricular block second degree	0/288 (0%)	0	1/146 (0.7%)	1
Cardiac failure congestive	1/288 (0.3%)	1	0/146 (0%)	0
Supraventricular tachycardia	1/288 (0.3%)	1	0/146 (0%)	0
Ear and labyrinth disorders
Vertigo positional	1/288 (0.3%)	1	0/146 (0%)	0
Eye disorders
Normal tension glaucoma	1/288 (0.3%)	1	0/146 (0%)	0
Gastrointestinal disorders
Gastritis	1/288 (0.3%)	1	0/146 (0%)	0
Impaired gastric emptying	0/288 (0%)	0	1/146 (0.7%)	1
General disorders
Pyrexia	1/288 (0.3%)	1	0/146 (0%)	0
Infections and infestations
Anal abscess	1/288 (0.3%)	1	0/146 (0%)	0
Bronchitis	0/288 (0%)	0	1/146 (0.7%)	1
Dengue fever	0/288 (0%)	0	1/146 (0.7%)	1
Meningitis haemophilus	1/288 (0.3%)	1	0/146 (0%)	0
Pyelonephritis chronic	1/288 (0.3%)	2	0/146 (0%)	0
Injury, poisoning and procedural complications
Fall	2/288 (0.7%)	2	0/146 (0%)	0
Fibula fracture	1/288 (0.3%)	1	0/146 (0%)	0
Humerus fracture	1/288 (0.3%)	1	0/146 (0%)	0
Stab wound	0/288 (0%)	0	1/146 (0.7%)	1
Investigations
Amylase increased	1/288 (0.3%)	1	0/146 (0%)	0
Lipase increased	1/288 (0.3%)	1	0/146 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/288 (0.3%)	1	0/146 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pleural mesothelioma malignant	1/288 (0.3%)	1	0/146 (0%)	0
Nervous system disorders
Hypoglycaemic unconsciousness	1/288 (0.3%)	1	0/146 (0%)	0
Thalamic infarction	1/288 (0.3%)	1	0/146 (0%)	0
Renal and urinary disorders
Renal cyst	1/288 (0.3%)	1	0/146 (0%)	0
Renal failure acute	1/288 (0.3%)	1	0/146 (0%)	0
Surgical and medical procedures
Coronary revascularisation	1/288 (0.3%)	1	0/146 (0%)	0
Vascular disorders
Hypotension	1/288 (0.3%)	1	0/146 (0%)	0
Other (Not Including Serious) Adverse Events
	IDegLira		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	83/288 (28.8%)		38/146 (26%)
Infections and infestations
Influenza	8/288 (2.8%)	8	8/146 (5.5%)	9
Nasopharyngitis	25/288 (8.7%)	29	12/146 (8.2%)	15
Investigations
Lipase increased	27/288 (9.4%)	29	6/146 (4.1%)	8
Metabolism and nutrition disorders
Dyslipidaemia	19/288 (6.6%)	19	6/146 (4.1%)	7
Nervous system disorders
Headache	15/288 (5.2%)	18	8/146 (5.5%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone pubication and/or communication for up to 60 days to protect intellectual property.