DUAL™ V: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide Versus Insulin Glargine in Subjects With Type 2 Diabetes Mellitus

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01952145
• Collaborator: (none)
• Enrollment: 557
• Locations: 91
• Arms: 2
• Actual Duration (Months): 13.5
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of the trial is to compare the efficacy and safety of insulin degludec/liraglutide versus insulin glargine in subjects with type 2 diabetes mellitus.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 557 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide Versus Insulin Glargine in Subjects With Type 2 Diabetes Mellitus (DUAL™ V - Basal Insulin Switch)
• Actual Study Start Date: Sep 20, 2013
• Actual Primary Completion Date: Nov 4, 2014
• Actual Study Completion Date: Nov 4, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin degludec/liraglutide OD plus metformin	Drug: insulin degludec/liraglutide; Insulin degludec/liraglutide is injected subcutaneously s.c. (under the skin) once daily (OD). Dose individually adjusted. Subjects should continue their pre-trial treatment with metformin.
Active Comparator: Insulin glargine OD plus metformin	Drug: insulin glargine; Insulin glargine is injected subcutaneously s.c. (under the skin) once daily (OD). Dose individually adjusted. Subjects should continue their pre-trial treatment with metformin.

Outcome Measures

Primary Outcome Measures

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

   Change from baseline in HbA1c after 26 weeks of treatment

Secondary Outcome Measures

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

   Change from baseline in body weight after 26 weeks of treatment

2. Number of Treatment Emergent Confirmed Hypoglycaemic Episodes [During 26 weeks of treatment]

   Confirmed hypoglycaemic episodes were defined as either: Severe (i.e., an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions) or an episode biochemically confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia.

Eligibility Criteria

Criteria

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

Inclusion Criteria: - Type 2 diabetes mellitus - HbA1c 7.0-10.0% [53-86 mmol/mol] (both inclusive) by central laboratory analysis - Current treatment with insulin glargine for at least 90 days prior to screening - Stable daily dose of insulin glargine between 20 units and 50 units (both inclusive) for at least 56 days prior to screening. Total daily dose should be within the range of 20-50 units, both inclusive, on the day of screening, but individual fluctuations of plus/minus 10 procent within the 56 days prior to screening are acceptable - Stable daily dose of metformin (above or equal to 1500 mg or max tolerated dose) for at least 90 days prior to screening - Body mass index (BMI) below or equal to 40 kg/m^2 Exclusion Criteria: - Any use of oral antidiabetic agents (OADs) (except for metformin) within 90 days prior to Visit 1 (screening) - Current use of any drug (except metformin and insulin glargine) or anticipated change inconcomitant medication, which in the investigator's opinion could interfere with the glucose metabolism (e.g. systemic corticosteroids) - Previous and/or current treatment with any insulin regimen other than basal insulin, e.g. prandial or pre-mixed insulin (short term treatment due to intercurrent illness includinggestational diabetes is allowed at the discretion of the investigator) - Previous and/or current treatment with glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exenatide, liraglutide) - Impaired liver function, defined as ALAT (alanine aminotransferase) above or equal to 2.5 times upper normal range (UNR) - Impaired renal function defined as serum-creatinine above or equal to 133 micromol/L (above or equal to 1.5 mg/dL) for males and above or equal to 125 micromol/L (1.4 mg/dL) for females, or as allowed according to local contraindications for metformin - 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) - History of chronic pancreatitis or idiopathic acute pancreatitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Fresno	California	United States	93720
2	Novo Nordisk Investigational Site	Los Alamitos	California	United States	90720
3	Novo Nordisk Investigational Site	Palm Springs	California	United States	92262
4	Novo Nordisk Investigational Site	San Diego	California	United States	92111
5	Novo Nordisk Investigational Site	Colorado Springs	Colorado	United States	80906
6	Novo Nordisk Investigational Site	Colorado Springs	Colorado	United States	80909
7	Novo Nordisk Investigational Site	Bradenton	Florida	United States	34201
8	Novo Nordisk Investigational Site	Fort Lauderdale	Florida	United States	33316
9	Novo Nordisk Investigational Site	Miami	Florida	United States	33165
10	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33027
11	Novo Nordisk Investigational Site	Tampa	Florida	United States	33603
12	Novo Nordisk Investigational Site	Gurnee	Illinois	United States	60031
13	Novo Nordisk Investigational Site	Evansville	Indiana	United States	47725
14	Novo Nordisk Investigational Site	Michigan City	Indiana	United States	46360
15	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
16	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
17	Novo Nordisk Investigational Site	Slidell	Louisiana	United States	70461-4231
18	Novo Nordisk Investigational Site	Saint Charles	Missouri	United States	63303
19	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
20	Novo Nordisk Investigational Site	Franklin	Ohio	United States	45005
21	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73103
22	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73104
23	Novo Nordisk Investigational Site	Altoona	Pennsylvania	United States	16602
24	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19140
25	Novo Nordisk Investigational Site	Collierville	Tennessee	United States	38017
26	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
27	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
28	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78224
29	Novo Nordisk Investigational Site	West Jordan	Utah	United States	84088-8871
30	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
31	Novo Nordisk Investigational Site	Spokane	Washington	United States	99218
32	Novo Nordisk Investigational Site	Buenos Aires		Argentina	B1704ETD
33	Novo Nordisk Investigational Site	Capital Federal		Argentina	C1056ABJ
34	Novo Nordisk Investigational Site	Corrientes		Argentina	3400
35	Novo Nordisk Investigational Site	Salta		Argentina	4400
36	Novo Nordisk Investigational Site	Zarate		Argentina	B2800DGH
37	Novo Nordisk Investigational Site	Blacktown	New South Wales	Australia	2148
38	Novo Nordisk Investigational Site	Wollongong	New South Wales	Australia	2500
39	Novo Nordisk Investigational Site	Herston	Queensland	Australia	4029
40	Novo Nordisk Investigational Site	Ipswich	Queensland	Australia	4305
41	Novo Nordisk Investigational Site	Robina	Queensland	Australia	4226
42	Novo Nordisk Investigational Site	East Ringwood	Victoria	Australia	3135
43	Novo Nordisk Investigational Site	Athens		Greece	GR-11527
44	Novo Nordisk Investigational Site	Athens		Greece	GR-14233
45	Novo Nordisk Investigational Site	Ioannina		Greece	45500
46	Novo Nordisk Investigational Site	Larissa		Greece	GR-41110
47	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54642
48	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-56403
49	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-57001
50	Novo Nordisk Investigational Site	Budapest		Hungary	H-1134
51	Novo Nordisk Investigational Site	Eger		Hungary	3300
52	Novo Nordisk Investigational Site	Gyor		Hungary	9024
53	Novo Nordisk Investigational Site	Gyula		Hungary	5700
54	Novo Nordisk Investigational Site	Miskolc		Hungary	3526
55	Novo Nordisk Investigational Site	Pachuca	Hidalgo	Mexico	42084
56	Novo Nordisk Investigational Site	Cuernavaca	Morelos	Mexico	62250
57	Novo Nordisk Investigational Site	Mexico City	México, D.F.	Mexico	03300
58	Novo Nordisk Investigational Site	Durango		Mexico	34000
59	Novo Nordisk Investigational Site	Monterrey		Mexico	64460
60	Novo Nordisk Investigational Site	Kazan		Russian Federation	420073
61	Novo Nordisk Investigational Site	Kirov		Russian Federation	610014
62	Novo Nordisk Investigational Site	Moscow		Russian Federation	117036
63	Novo Nordisk Investigational Site	Moscow		Russian Federation	123448
64	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630117
65	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194358
66	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	199034
67	Novo Nordisk Investigational Site	St. Petersburg		Russian Federation	194354
68	Novo Nordisk Investigational Site	Tomsk		Russian Federation	634041
69	Novo Nordisk Investigational Site	Tomsk		Russian Federation	634050
70	Novo Nordisk Investigational Site	Volgograd		Russian Federation	400131
71	Novo Nordisk Investigational Site	Vsevolozhsk		Russian Federation	188643
72	Novo Nordisk Investigational Site	Bardejov		Slovakia	08501
73	Novo Nordisk Investigational Site	Dolny Kubin		Slovakia	02601
74	Novo Nordisk Investigational Site	Kosice		Slovakia	040 11
75	Novo Nordisk Investigational Site	Kosice		Slovakia	04001
76	Novo Nordisk Investigational Site	Levice		Slovakia	93401
77	Novo Nordisk Investigational Site	Lubochna		Slovakia	03491
78	Novo Nordisk Investigational Site	Poprad		Slovakia	05801
79	Novo Nordisk Investigational Site	Povazska Bystrica		Slovakia	01701
80	Novo Nordisk Investigational Site	Prievidza		Slovakia	97101
81	Novo Nordisk Investigational Site	Trnava		Slovakia	91701
82	Novo Nordisk Investigational Site	Velky Meder		Slovakia	93201
83	Novo Nordisk Investigational Site	Midrand	Gauteng	South Africa	1685
84	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4450
85	Novo Nordisk Investigational Site	Alberton		South Africa	1449
86	Novo Nordisk Investigational Site	Almería		Spain	04001
87	Novo Nordisk Investigational Site	Granada		Spain	18012
88	Novo Nordisk Investigational Site	Palma de Mallorca		Spain	07014
89	Novo Nordisk Investigational Site	Sevilla		Spain	41003
90	Novo Nordisk Investigational Site	Sevilla		Spain	41010
91	Novo Nordisk Investigational Site	Valencia		Spain	46026

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: NCT01952145
• Other Study ID Numbers: NN9068-3952; 2012-004413-14; U1111-1135-1003
• First Posted: Sep 27, 2013
• Last Update Posted: Jan 3, 2019
• Last Verified: Dec 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine; Liraglutide; Xultophy

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 75 sites in 10 countries as follows: Argentina: 5 sites; Australia: 4 sites; Greece: 6 sites, Hungary: 4 sites; Mexico: 5 sites, Russian Federation: 11 sites; Slovakia: 11 sites, South Africa: 4 sites; Spain: 6 sites, United States: 19 sites.
Pre-assignment Detail	Subjects who were recruited had T2DM and were required to have been on treatment with stable daily dose of insulin glargine between 20 units and 50 units (both inclusive) for at least 56 days prior to screening in combination with a stable daily dose of metformin (≥1500 mg or max tolerated dose) for at least 90 days prior to screening.

Arm/Group Title	Insulin Degludec/Liraglutide (IDegLira)	Insulin Glargine (IGlar)
Arm/Group Description	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.	Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.
Period Title: Overall Study
STARTED	278	279
COMPLETED	250	265
NOT COMPLETED	28	14

Baseline Characteristics

Arm/Group Title	Insulin Degludec/Liraglutide (IDegLira)	Insulin Glargine (IGlar)	Total
Arm/Group Description	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.	Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.	Total of all reporting groups
Overall Participants	278	279	557
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.4 (9.8)	59.1 (9.3)	58.8 (9.5)
Sex: Female, Male (Count of Participants)
Female	135 48.6%	142 50.9%	277 49.7%
Male	143 51.4%	137 49.1%	280 50.3%
Glycated hemoglobin (HbA1c) (Percentage (%)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage (%)]	8.4 (0.9)	8.2 (0.9)	8.3 (0.9)
Body weight (Kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg]	88.3 (17.5)	87.3 (15.8)	87.8 (16.6)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS was used for analysis of this endpoint. And FAS included all randomised subjects. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.

Arm/Group Title	Insulin Degludec/Liraglutide (IDegLira)	Insulin Glargine (IGlar)
Arm/Group Description	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.	Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.
Measure Participants	278	279
Mean (Standard Deviation) [Percentage (%)]	-1.81 (1.08)	-1.13 (0.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec/Liraglutide (IDegLira), Insulin Glargine (IGlar)
	Comments	This primary endpoint was analysed on the FAS using an ANCOVA model with treatment and region as fixed effects and baseline HbA1c value as covariate.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority of IDegLira versus IGlar was considered as confirmed, if the 95% confidence interval (CI) for the mean treatment difference was entirely below 0.30%.
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment contrast
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -0.74 to -0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS which included all randomised subjects was used for analysis of this endpoint. Missing values (including intermittent missing values) were imputed using LOCF method.

Arm/Group Title	Insulin Degludec/Liraglutide (IDegLira)	Insulin Glargine (IGlar)
Arm/Group Description	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.	Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.
Measure Participants	278	279
Mean (Standard Deviation) [Kg]	-1.4 (3.5)	1.8 (3.6)

3. Secondary Outcome

Title	Number of Treatment Emergent Confirmed Hypoglycaemic Episodes
Description	Confirmed hypoglycaemic episodes were defined as either: Severe (i.e., an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions) or an episode biochemically confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia.
Time Frame	During 26 weeks of treatment

Outcome Measure Data

Analysis Population Description

The safety analysis set was used for analysis of this endpoint and this set included all subjects receiving at least one dose of trial product. Subjects contributed to the evaluation "as treated". Confirmed hypoglycaemic episodes were reported by 79 subjects in IdegLira arm and by 137 subjects in IGlar arm.

Arm/Group Title	Insulin Degludec/Liraglutide (IDegLira)	Insulin Glargine (IGlar)
Arm/Group Description	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.	Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.
Measure Participants	278	279
Number [Number of episodes]	289	683

Adverse Events

Time Frame	Week 0 to week 27 (26-week treatment period and a follow-up visit 1 week after end of treatment)
Adverse Event Reporting Description	All AEs described below are treatment-emergent. A treatment-emergent AE (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. Analysis population: safety analysis set.
Arm/Group Title	Insulin Degludec/Liraglutide (IDegLira)		Insulin Glargine (IGlar)
Arm/Group Description	Eligible subjects received IDegLira once daily (OD) subcutaneously for a duration of 26 weeks. The starting dose of IDegLira was 16 dose steps (16 units IDeg/0.6 mg liraglutide) and was titrated according to a predefined titration algorithm with a maximum dose of 50 dose steps (50 units IDeg/1.8 mg liraglutide). Adjustment of the dose was performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days. Adjustments were made in increments or decrements of 2 dose steps, aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). That is, the adjustments were +2 or -2 if the mean of 3 pre-breakfast SMPG values were >5.0 mmol/L (or >90 mg/dL) and <4.0 mmol/L (or <71 mg/dL) respectively. No adjustment was done when the mean of 3 pre-breakfast SMPG values were 4.0 - 5.0 mmol/L (or 71-90 mg/dL). The subjects continued with pre-trial doses of metformin, unless there was a safety concern.		Eligible subjects received IGlar OD subcutaneously for a duration of 26 weeks. The treatment started with dose equal to the pre-trial daily dose (dose-to-dose switch), after which the dose was titrated according to the specified titration algorithm aiming at a fasting glycaemic target of 4.0-5.0 mmol/L (71-90 mg/dL). No predefined maximum dose was specified for IGlar. The subjects continued with pre-trial doses of metformin, unless there was a safety concern.
All Cause Mortality
	Insulin Degludec/Liraglutide (IDegLira)		Insulin Glargine (IGlar)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin Degludec/Liraglutide (IDegLira)		Insulin Glargine (IGlar)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/278 (1.8%)		9/279 (3.2%)
Cardiac disorders
Acute coronary syndrome	0/278 (0%)	0	1/279 (0.4%)	1
Arrhythmia	0/278 (0%)	0	1/279 (0.4%)	1
Cardiac failure	0/278 (0%)	0	1/279 (0.4%)	1
Ear and labyrinth disorders
Auricular perichondritis	0/278 (0%)	0	1/279 (0.4%)	1
Hepatobiliary disorders
Biliary colic	0/278 (0%)	0	1/279 (0.4%)	1
Cholecystitis acute	0/278 (0%)	0	1/279 (0.4%)	1
Cholelithiasis	1/278 (0.4%)	1	0/279 (0%)	0
Infections and infestations
Appendicitis	0/278 (0%)	0	1/279 (0.4%)	1
Metabolism and nutrition disorders
Hypoglycaemia	0/278 (0%)	0	1/279 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	1/278 (0.4%)	1	0/279 (0%)	0
Rectal adenocarcinoma	1/278 (0.4%)	1	0/279 (0%)	0
Nervous system disorders
Haemorrhagic stroke	0/278 (0%)	0	1/279 (0.4%)	1
Vertebrobasilar insufficiency	1/278 (0.4%)	1	0/279 (0%)	0
Reproductive system and breast disorders
Postmenopausal haemorrhage	1/278 (0.4%)	1	0/279 (0%)	0
Other (Not Including Serious) Adverse Events
	Insulin Degludec/Liraglutide (IDegLira)		Insulin Glargine (IGlar)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/278 (18.7%)		22/279 (7.9%)
Gastrointestinal disorders
Diarrhoea	20/278 (7.2%)	23	7/279 (2.5%)	10
Nausea	26/278 (9.4%)	34	3/279 (1.1%)	3
Vomiting	14/278 (5%)	22	5/279 (1.8%)	5
Nervous system disorders
Headache	11/278 (4%)	12	14/279 (5%)	28

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 publication and/or communication for up to 60 days to protect intellectual property.