A Study to Determine the Efficacy and Safety of Albiglutide as Compared With Liraglutide.

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01128894
• Collaborator: (none)
• Enrollment: 841
• Locations: 174
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This open-label study examines the efficacy and safety of albiglutide as compared with liraglutide in subjects with type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Biological: albiglutide; Drug: liraglutide	Phase 3

Detailed Description

This randomized, open-label, multicenter, 2 parallel-group study evaluates the efficacy and safety of a weekly subcutaneously injected dose of albiglutide as compared with liraglutide. Subjects with a historical diagnosis of type 2 diabetes mellitus and whose glycemia is inadequately controlled on their current regimen of metformin, thiazolidinedione, sulfonylurea, or any combination of these oral antidiabetics will be recruited into the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 841 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Parallel-Group, Multicenter Study to Determine the Efficacy and Safety of Albiglutide as Compared With Liraglutide in Subjects With Type 2 Diabetes Mellitus
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: albiglutide weekly albiglutide subcutaneous injection	Biological: albiglutide; albiglutide weekly subcutaneous injection
Active Comparator: liraglutide liraglutide daily subcutaneous injection, starting at 0.6mg, then up-titrating to 1.2mg then 1.8mg in accordance with prescribing information.	Drug: liraglutide; liraglutide daily subcutaneous injection, starting at 0.6mg, then up-titrating to 1.2mg then 1.8mg in accordance with prescribing information.

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 32 [Baseline and Week 32]

   HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline in HbA1c was calculated as the value at Week 32 minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, history of prior myocardial infarction (yes versus no), and age category (<65 years versus ≥65 years) as factors and Baseline HbA1c as a continuous covariate. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.

Secondary Outcome Measures

1. Mean Change From Baseline in HbA1c at Weeks 4, 6, 12, 18 and 26 [Baseline, Weeks 4, 6, 12, 18 and 26]

   HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. Participants were considered in the treatment week if they had received at least one dose in that treatment week.

2. Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32 [Baseline and Week 32]

   The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, Baseline HbA1c category, history of prior myocardial infarction (yes versus no), and age category (<65 years versus ≥65 years) as factors and Baseline FPG as a continuous covariate. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. Participants were considered in the treatment week if they had received at least one dose in that treatment week.

3. Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 1, 2, 3, 4, 6, 12, 18 and 26 [Baseline, Weeks 1, 2, 3, 4, 6, 12, 18 and 26]

   The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. Participants were considered in the treatment week if they had received at least one dose in that treatment week.

4. Number of Participants Who Achieved HbA1c Response Level of <6.5% and <7.0% at Week 32 [Week 32]

   Number of participants who achieved HbA1c response levels of <6.5% and <7.0% at Week 32 were assessed. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.

5. Time to Hyperglycemia Rescue at Week 32 [Week 32]

   Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia rescue were as follows: fasting plasma glucose (FPG) >=280 milligram/decilitre (mg/dL) >= Week 2 and < Week 4, FPG >=250 mg/dL >= Week 4 and <Week 12, HbA1c ≥8.5% and ≤0.5% reduction from Baseline- >= Week 12 and <Week 26, or HbA1c ≥8.5% >= Week 26. Time to hyperglycemia rescue is defined as the time between the date of the first dose of study medication and the date of hyperglycemia rescue plus one day, or the time between the date of the first dose of study medication and the date of the last visit during the active treatment period plus one day for participants not requiring rescue. This time was divided by 7 to express the result in weeks. All times extending beyond Week 32 relevant to hyperglycemia rescue were censored at Week 32.

6. Mean Change From Baseline in Body Weight at Week 32 [Baseline and Week 32]

   The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the value at Week 32 minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, Baseline HbA1c category, history of prior myocardial infarction (yes versus no), and age category (<65 years versus ≥65 years) as factors and Baseline weight as a continuous covariate. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. Weight values obtained after hyperglycemia rescue were treated as missing and replaced with pre-rescue values.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of type 2 diabetes mellitus and experiencing inadequate glycemic control on their current regimen of metformin, TZD, SU, or any combination of these oral antidiabetic medications

• BMI >/=20kg/m2 and </=45 kg/m2

• Fasting C-peptide >/=0.8 ng/mL (>/=0.26 nmol/L)

• HbA1c between 7.0% and 10.0%, inclusive

• Female subjects of childbearing potential must be practicing adequate contraception.

Exclusion Criteria:

• History of cancer

• History of treated diabetic gastroparesis

• Current biliary disease or history of pancreatitis

• History of significant GI surgery

• Recent clinically significant cardiovascular and/or cerebrovascular disease

• Hypertension

• History of human immunodeficiency virus infection

• History of or current liver disease or acute symptomatic infection with hepatitis B or hepatitis C

• History of alcohol or substance abuse

• Female subject is pregnant, lactating, or <6 weeks postpartum

• Known allergy to any GLP 1 analogue, liraglutide, other study medications' excipients, excipients of albiglutide, or Baker's yeast

• History of type 1 diabetes mellitus

• Contraindications (as per the prescribing information) for the use of either background or potential randomized study medications (e.g., liraglutide)

• Receipt of any investigational drug or liraglutide within the 30 days or 5 half lives, whichever is longer, before Screening or a history of receipt of an investigational antidiabetic drug within the 3 months before randomization or receipt of albiglutide in previous studies

• History or family history of thyroid disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35294
2	GSK Investigational Site	Chandler	Arizona	United States	85224
3	GSK Investigational Site	Gilbert	Arizona	United States	85295
4	GSK Investigational Site	Phoenix	Arizona	United States	85032
5	GSK Investigational Site	Tucson	Arizona	United States	85712
6	GSK Investigational Site	Searcy	Arkansas	United States	72143
7	GSK Investigational Site	Chula Vista	California	United States	91910
8	GSK Investigational Site	Escondido	California	United States	92026
9	GSK Investigational Site	Fresno	California	United States	93720
10	GSK Investigational Site	Huntington Beach	California	United States	92648
11	GSK Investigational Site	Indio	California	United States	92201
12	GSK Investigational Site	Irvine	California	United States	92618
13	GSK Investigational Site	Los Angeles	California	United States	90017
14	GSK Investigational Site	Los Angeles	California	United States	90022
15	GSK Investigational Site	Mission Viejo	California	United States	92691
16	GSK Investigational Site	Orange	California	United States	92868
17	GSK Investigational Site	Palm Desert	California	United States	92260
18	GSK Investigational Site	Riverside	California	United States	92506
19	GSK Investigational Site	San Diego	California	United States	92120
20	GSK Investigational Site	San Diego	California	United States	92128
21	GSK Investigational Site	Satna Monica	California	United States	90404
22	GSK Investigational Site	Spring Valley	California	United States	91978
23	GSK Investigational Site	Tarzana	California	United States	91356
24	GSK Investigational Site	Tustin	California	United States	92780
25	GSK Investigational Site	Walnut Creek	California	United States	94598
26	GSK Investigational Site	West Hills	California	United States	91307
27	GSK Investigational Site	Clearwater	Florida	United States	33765
28	GSK Investigational Site	Cocoa	Florida	United States	32927
29	GSK Investigational Site	Miami	Florida	United States	33156
30	GSK Investigational Site	North Miami	Florida	United States	33161
31	GSK Investigational Site	Ocala	Florida	United States	34471
32	GSK Investigational Site	Orlando	Florida	United States	32822
33	GSK Investigational Site	Pembroke Pines	Florida	United States	33026
34	GSK Investigational Site	St. Petersburg	Florida	United States	33709
35	GSK Investigational Site	Tampa	Florida	United States	33613
36	GSK Investigational Site	Winter Park	Florida	United States	32789
37	GSK Investigational Site	Winter Park	Florida	United States	32792
38	GSK Investigational Site	Atlanta	Georgia	United States	30309
39	GSK Investigational Site	Atlanta	Georgia	United States	30312
40	GSK Investigational Site	Atlanta	Georgia	United States	30338
41	GSK Investigational Site	Atlanta	Georgia	United States	30342
42	GSK Investigational Site	Blue Ridge	Georgia	United States	30513
43	GSK Investigational Site	Roswell	Georgia	United States	30076
44	GSK Investigational Site	Stone Mountain	Georgia	United States	30088
45	GSK Investigational Site	Honolulu	Hawaii	United States	96814
46	GSK Investigational Site	Idaho Falls	Idaho	United States	83404
47	GSK Investigational Site	La Grange	Illinois	United States	60525
48	GSK Investigational Site	Evansville	Indiana	United States	47714
49	GSK Investigational Site	Valparaiso	Indiana	United States	46383
50	GSK Investigational Site	Council Bluffs	Iowa	United States	51501
51	GSK Investigational Site	Dubuque	Iowa	United States	52001
52	GSK Investigational Site	Lexington	Kentucky	United States	40504
53	GSK Investigational Site	Paducah	Kentucky	United States	42003
54	GSK Investigational Site	Covington	Louisiana	United States	70433
55	GSK Investigational Site	Shreveport	Louisiana	United States	71101
56	GSK Investigational Site	Haverhill	Massachusetts	United States	01830
57	GSK Investigational Site	Bloomfield Hills	Michigan	United States	48302
58	GSK Investigational Site	Dearborn	Michigan	United States	48124
59	GSK Investigational Site	Detroit	Michigan	United States	48235
60	GSK Investigational Site	Kalamazoo	Michigan	United States	49009
61	GSK Investigational Site	Kalamazoo	Michigan	United States	49048
62	GSK Investigational Site	St Clair Shores	Michigan	United States	48081
63	GSK Investigational Site	Minneapolis	Minnesota	United States	55430
64	GSK Investigational Site	Picayune	Mississippi	United States	39466
65	GSK Investigational Site	Kansas City	Missouri	United States	64111
66	GSK Investigational Site	St. Louis	Missouri	United States	63110
67	GSK Investigational Site	St. Louis	Missouri	United States	63141
68	GSK Investigational Site	Lincoln	Nebraska	United States	68516
69	GSK Investigational Site	Omaha	Nebraska	United States	68131
70	GSK Investigational Site	Las Vegas	Nevada	United States	89102
71	GSK Investigational Site	Las Vegas	Nevada	United States	89103
72	GSK Investigational Site	Elizabeth	New Jersey	United States	07202
73	GSK Investigational Site	Haddon Heights	New Jersey	United States	08035
74	GSK Investigational Site	North Massapequa	New York	United States	11758
75	GSK Investigational Site	Staten Island	New York	United States	10301
76	GSK Investigational Site	Burlington	North Carolina	United States	27215
77	GSK Investigational Site	Durham	North Carolina	United States	27710
78	GSK Investigational Site	Greensboro	North Carolina	United States	27405
79	GSK Investigational Site	Lenoir	North Carolina	United States	28645
80	GSK Investigational Site	Morehead City	North Carolina	United States	28557
81	GSK Investigational Site	Shelby	North Carolina	United States	28150
82	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
83	GSK Investigational Site	Canal Fulton	Ohio	United States	44614
84	GSK Investigational Site	Cleveland	Ohio	United States	44122
85	GSK Investigational Site	Columbus	Ohio	United States	43213
86	GSK Investigational Site	Dayton	Ohio	United States	45439
87	GSK Investigational Site	Gallipolis	Ohio	United States	45631
88	GSK Investigational Site	Kettering	Ohio	United States	45429
89	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73103
90	GSK Investigational Site	Portland	Oregon	United States	97239
91	GSK Investigational Site	Downington	Pennsylvania	United States	19335
92	GSK Investigational Site	Greer	South Carolina	United States	29651
93	GSK Investigational Site	Murrells Inlet	South Carolina	United States	29576
94	GSK Investigational Site	Simpsonville	South Carolina	United States	29681
95	GSK Investigational Site	Bristol	Tennessee	United States	37620
96	GSK Investigational Site	Clarksville	Tennessee	United States	37043
97	GSK Investigational Site	Memphis	Tennessee	United States	38125
98	GSK Investigational Site	Tullahoma	Tennessee	United States	37398
99	GSK Investigational Site	Arlington	Texas	United States	76012
100	GSK Investigational Site	Corpus Christi	Texas	United States	78404
101	GSK Investigational Site	Dallas	Texas	United States	75230
102	GSK Investigational Site	Dallas	Texas	United States	75246
103	GSK Investigational Site	Dallas	Texas	United States	75251
104	GSK Investigational Site	Fort Worth	Texas	United States	76104
105	GSK Investigational Site	Houston	Texas	United States	77036
106	GSK Investigational Site	Houston	Texas	United States	77074
107	GSK Investigational Site	Houston	Texas	United States	77088
108	GSK Investigational Site	Hurst	Texas	United States	76054
109	GSK Investigational Site	Katy	Texas	United States	77450
110	GSK Investigational Site	Midland	Texas	United States	79707
111	GSK Investigational Site	North Richland Hills	Texas	United States	76180
112	GSK Investigational Site	San Antonio	Texas	United States	78215
113	GSK Investigational Site	San Antonio	Texas	United States	78217
114	GSK Investigational Site	San Antonio	Texas	United States	78229
115	GSK Investigational Site	San Antonio	Texas	United States	78237
116	GSK Investigational Site	Schertz	Texas	United States	78154
117	GSK Investigational Site	Sugarland	Texas	United States	77479
118	GSK Investigational Site	Bountiful	Utah	United States	84010
119	GSK Investigational Site	Draper	Utah	United States	84020
120	GSK Investigational Site	West Jordan	Utah	United States	84088
121	GSK Investigational Site	South Burlington	Vermont	United States	05403
122	GSK Investigational Site	Burke	Virginia	United States	22015
123	GSK Investigational Site	Manassas	Virginia	United States	20110
124	GSK Investigational Site	Richmond	Virginia	United States	23225
125	GSK Investigational Site	Richmond	Virginia	United States	23294
126	GSK Investigational Site	Salem	Virginia	United States	24153
127	GSK Investigational Site	Spokane	Washington	United States	99208
128	GSK Investigational Site	Spokane	Washington	United States	99216
129	GSK Investigational Site	Tacoma	Washington	United States	98405
130	GSK Investigational Site	Garran	Australian Capital Territory	Australia	2606
131	GSK Investigational Site	Camperdown	New South Wales	Australia	2050
132	GSK Investigational Site	St Leonards	New South Wales	Australia	2065
133	GSK Investigational Site	Herston	Queensland	Australia	4029
134	GSK Investigational Site	Box Hill	Victoria	Australia	3128
135	GSK Investigational Site	Geelong	Victoria	Australia	3220
136	GSK Investigational Site	Heidelberg	Victoria	Australia	3081
137	GSK Investigational Site	Ringwood East	Victoria	Australia	3135
138	GSK Investigational Site	Fremantle	Western Australia	Australia	6160
139	GSK Investigational Site	Beer-Sheva		Israel	84101
140	GSK Investigational Site	Haifa		Israel	35251
141	GSK Investigational Site	Kfar Saba		Israel	44281
142	GSK Investigational Site	Nahariya		Israel	22100
143	GSK Investigational Site	Goyang		Korea, Republic of	414410
144	GSK Investigational Site	Seongnam-si,		Korea, Republic of	463-707
145	GSK Investigational Site	Seongnam-si		Korea, Republic of	463712
146	GSK Investigational Site	Seoul		Korea, Republic of	135720
147	GSK Investigational Site	Seoul		Korea, Republic of	136-705
148	GSK Investigational Site	Seoul		Korea, Republic of	137-701
149	GSK Investigational Site	Seoul		Korea, Republic of	139-872
150	GSK Investigational Site	Callao	Lima	Peru	Callao 2
151	GSK Investigational Site	Huacho	Lima	Peru
152	GSK Investigational Site	Ica		Peru	11
153	GSK Investigational Site	Lima		Peru	01
154	GSK Investigational Site	Lima		Peru	17
155	GSK Investigational Site	Lima		Peru	Lima 1
156	GSK Investigational Site	Piura		Peru
157	GSK Investigational Site	Cebu City		Philippines	6000
158	GSK Investigational Site	Iloilo City		Philippines	5000
159	GSK Investigational Site	Makati City		Philippines	1218
160	GSK Investigational Site	Marikina City		Philippines	1810
161	GSK Investigational Site	Pasay		Philippines	1300
162	GSK Investigational Site	Pasig City		Philippines	1600
163	GSK Investigational Site	Pasig		Philippines	1600
164	GSK Investigational Site	Alicante		Spain	03114
165	GSK Investigational Site	La Coruña		Spain	15006
166	GSK Investigational Site	Majadahonda (Madrid)		Spain	28222
167	GSK Investigational Site	Modulo H		Spain	07120
168	GSK Investigational Site	Sabadell		Spain	08208
169	GSK Investigational Site	Torrevieja (Alicante)		Spain	03186
170	GSK Investigational Site	Birmingham		United Kingdom	B9 5SS
171	GSK Investigational Site	Hertfordshire		United Kingdom
172	GSK Investigational Site	Livingston		United Kingdom	EH54 6PP
173	GSK Investigational Site	London		United Kingdom	SE1 9RT
174	GSK Investigational Site	Swansea		United Kingdom	SA6 6NL

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01128894
• Other Study ID Numbers: 114179
• First Posted: May 24, 2010
• Last Update Posted: Feb 23, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: GSK716155; liraglutide; albiglutide; open-label
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Liraglutide; rGLP-1 protein

Study Results

Participant Flow

Pre-assignment Detail	Eligible participants entered into 2 weeks of Prescreening and Screening; 4 weeks of Run-in/stabilization; a 32-week Treatment Period for evaluation of efficacy and safety and 8 weeks of post treatment Follow-up. A total of 1764 participants were screened, 841 were randomized and 812 received at least one dose of study treatment.

Arm/Group Title	Albiglutide 50 mg	Liraglutide 1.8 mg
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.	Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.
Period Title: Overall Study
STARTED	404	408
COMPLETED	346	340
NOT COMPLETED	58	68

Baseline Characteristics

Arm/Group Title	Albiglutide 50 mg	Liraglutide 1.8 mg	Total
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.	Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.	Total of all reporting groups
Overall Participants	404	408	812
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.4 (10.11)	55.8 (9.95)	55.6 (10.03)
Gender (Count of Participants)
Female	213 52.7%	190 46.6%	403 49.6%
Male	191 47.3%	218 53.4%	409 50.4%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	47 11.6%	29 7.1%	76 9.4%
American Indian or Alaskan Native	30 7.4%	37 9.1%	67 8.3%
Asian - Central/South Asian Heritage	3 0.7%	9 2.2%	12 1.5%
Asian - East Asian Heritage	26 6.4%	18 4.4%	44 5.4%
Asian - Japanese Heritage	0 0%	3 0.7%	3 0.4%
Asian - South East Asian Heritage	17 4.2%	19 4.7%	36 4.4%
Native Hawaiian or Other Pacific Islander	0 0%	2 0.5%	2 0.2%
White - Arabic/North African Heritage	5 1.2%	6 1.5%	11 1.4%
White - White/Caucasian/European Heritage	276 68.3%	285 69.9%	561 69.1%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 32
Description	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline in HbA1c was calculated as the value at Week 32 minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, history of prior myocardial infarction (yes versus no), and age category (<65 years versus ≥65 years) as factors and Baseline HbA1c as a continuous covariate. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.
Time Frame	Baseline and Week 32

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study medication and who had at least one post-Baseline assessment of the primary endpoint, HbA1c. Only those participants available at the indicated time point were assessed.

Arm/Group Title	Albiglutide 50 mg	Liraglutide 1.8 mg
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.	Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.
Measure Participants	398	402
Least Squares Mean (Standard Error) [Percentage of HbA1c in the blood]	-0.78 (0.047)	-0.99 (0.046)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albiglutide 50 mg, Liraglutide 1.8 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The p-value was from a 1-sided t test testing whether or not the difference of least square means (albiglutide - liraglutide) was less than or equal to the prespecified noninferiority margin of 0.3%.
Statistical Test of Hypothesis	p-Value	0.0846
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; 0.08 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Change From Baseline in HbA1c at Weeks 4, 6, 12, 18 and 26
Description	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. Participants were considered in the treatment week if they had received at least one dose in that treatment week.
Time Frame	Baseline, Weeks 4, 6, 12, 18 and 26

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	Albiglutide 50 mg	Liraglutide 1.8 mg
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.	Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.
Measure Participants	402	403
Week 4, n=387, 392	-0.52 (0.481)	-0.73 (0.447)
Week 6, n=398, 401	-0.66 (0.566)	-0.94 (0.569)
Week 12, n=398, 402	-0.88 (0.824)	-1.18 (0.798)
Week 18, n=398, 402	-0.87 (0.921)	-1.13 (0.904)
Week 26, n=398, 402	-0.79 (0.968)	-1.00 (0.969)

3. Secondary Outcome

Title	Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32
Description	The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, Baseline HbA1c category, history of prior myocardial infarction (yes versus no), and age category (<65 years versus ≥65 years) as factors and Baseline FPG as a continuous covariate. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. Participants were considered in the treatment week if they had received at least one dose in that treatment week.
Time Frame	Baseline and Week 32

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time point were assessed.

Arm/Group Title	Albiglutide 50 mg	Liraglutide 1.8 mg
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.	Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.
Measure Participants	400	402
Least Squares Mean (Standard Error) [Millimoles per liter (mmol/L)]	-1.22 (0.115)	-1.68 (0.115)

4. Secondary Outcome

Title	Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 1, 2, 3, 4, 6, 12, 18 and 26
Description	The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. Participants were considered in the treatment week if they had received at least one dose in that treatment week.
Time Frame	Baseline, Weeks 1, 2, 3, 4, 6, 12, 18 and 26

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	Albiglutide 50 mg	Liraglutide 1.8 mg
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.	Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.
Measure Participants	402	403
Week 1, n=386, 381	-0.98 (1.939)	-1.62 (2.116)
Week 2, n= 399, 398	-1.33 (2.194)	-2.25 (2.296)
Week 3, n= 400, 402	-1.61 (2.067)	-2.43 (2.470)
Week 4, n= 400, 402	-1.52 (2.148)	-2.45 (2.381)
Week 6, n= 400, 402	-1.25 (2.317)	-2.11 (2.451)
Week 12, n= 400, 402	-1.73 (2.526)	-2.10 (2.590)
Week 18, n= 400, 402	-1.44 (2.362)	-1.74 (2.704)
Week 26, n= 400, 402	-1.14 (2.694)	-1.64 (2.717)

5. Secondary Outcome

Title	Number of Participants Who Achieved HbA1c Response Level of <6.5% and <7.0% at Week 32
Description	Number of participants who achieved HbA1c response levels of <6.5% and <7.0% at Week 32 were assessed. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.
Time Frame	Week 32

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time point were assessed.

Arm/Group Title	Albiglutide 50 mg	Liraglutide 1.8 mg
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.	Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.
Measure Participants	398	402
HbA1c <6.5%	78 19.3%	113 27.7%
HbA1c <7.0%	168 41.6%	208 51%

6. Secondary Outcome

Title	Time to Hyperglycemia Rescue at Week 32
Description	Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia rescue were as follows: fasting plasma glucose (FPG) >=280 milligram/decilitre (mg/dL) >= Week 2 and < Week 4, FPG >=250 mg/dL >= Week 4 and <Week 12, HbA1c ≥8.5% and ≤0.5% reduction from Baseline- >= Week 12 and <Week 26, or HbA1c ≥8.5% >= Week 26. Time to hyperglycemia rescue is defined as the time between the date of the first dose of study medication and the date of hyperglycemia rescue plus one day, or the time between the date of the first dose of study medication and the date of the last visit during the active treatment period plus one day for participants not requiring rescue. This time was divided by 7 to express the result in weeks. All times extending beyond Week 32 relevant to hyperglycemia rescue were censored at Week 32.
Time Frame	Week 32

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Albiglutide 50 mg	Liraglutide 1.8 mg
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.	Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.
Measure Participants	402	403
Median (95% Confidence Interval) [Weeks]	NA	NA

7. Secondary Outcome

Title	Mean Change From Baseline in Body Weight at Week 32
Description	The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the value at Week 32 minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, Baseline HbA1c category, history of prior myocardial infarction (yes versus no), and age category (<65 years versus ≥65 years) as factors and Baseline weight as a continuous covariate. The LOCF method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. Weight values obtained after hyperglycemia rescue were treated as missing and replaced with pre-rescue values.
Time Frame	Baseline and Week 32

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time point were assessed.

Arm/Group Title	Albiglutide 50 mg	Liraglutide 1.8 mg
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.	Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.
Measure Participants	400	402
Mean (Standard Deviation) [Kilograms]	-0.62 (3.118)	-2.21 (4.147)

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occurring while participants were on treatment up until 56 days after the last dose (up to Week 40), are reported.
Adverse Event Reporting Description	SAEs and AEs were collected in members of the Safety Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Arm/Group Title	Albiglutide 50 mg		Liraglutide 1.8 mg
Arm/Group Description	Participants received albiglutide 30 milligrams (mg) once weekly subcutaneously (SC) from Baseline until Week 6 with up-titration to 50 mg weekly at Week 6.		Participants received liraglutide 0.6 mg once daily (OD) SC from Baseline until Week 1. From Week 1 to Week 2 the dose was increased to 1.2 mg. At Week 2, the dose was increased to 1.8 mg.
All Cause Mortality
	Albiglutide 50 mg		Liraglutide 1.8 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Albiglutide 50 mg		Liraglutide 1.8 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/404 (5%)		23/408 (5.6%)
Cardiac disorders
Atrial fibrillation	2/404 (0.5%)		2/408 (0.5%)
Myocardial infarction	1/404 (0.2%)		1/408 (0.2%)
Acute myocardial infarction	0/404 (0%)		1/408 (0.2%)
Arteriosclerosis coronary artery	1/404 (0.2%)		0/408 (0%)
Atrial flutter	1/404 (0.2%)		0/408 (0%)
Cardiac failure congestive	0/404 (0%)		1/408 (0.2%)
Coronary artery disease	0/404 (0%)		1/408 (0.2%)
Coronary artery occlusion	0/404 (0%)		1/408 (0.2%)
Ear and labyrinth disorders
Vertigo	0/404 (0%)		1/408 (0.2%)
Endocrine disorders
Hyperthyroidism	0/404 (0%)		1/408 (0.2%)
Eye disorders
Retinal detachment	0/404 (0%)		1/408 (0.2%)
Gastrointestinal disorders
Colitis	0/404 (0%)		1/408 (0.2%)
Pancreatitis	0/404 (0%)		1/408 (0.2%)
General disorders
Chest pain	1/404 (0.2%)		2/408 (0.5%)
Non-cardiac chest pain	1/404 (0.2%)		1/408 (0.2%)
Pyrexia	1/404 (0.2%)		0/408 (0%)
Sudden death	0/404 (0%)		1/408 (0.2%)
Ileus	0/404 (0%)		1/408 (0.2%)
Hepatobiliary disorders
Hepatitis	1/404 (0.2%)		0/408 (0%)
Infections and infestations
Gastroenteritis	2/404 (0.5%)		0/408 (0%)
Cellulitis	0/404 (0%)		1/408 (0.2%)
Encephalitis herpes	1/404 (0.2%)		0/408 (0%)
Influenza	1/404 (0.2%)		0/408 (0%)
Osteomyelitis	1/404 (0.2%)		0/408 (0%)
Pneumonia viral	1/404 (0.2%)		0/408 (0%)
Tracheobronchitis	0/404 (0%)		1/408 (0.2%)
Urinary tract infection	1/404 (0.2%)		0/408 (0%)
Viral infection	1/404 (0.2%)		0/408 (0%)
Injury, poisoning and procedural complications
Burns first degree	0/404 (0%)		1/408 (0.2%)
Subdural haematoma	0/404 (0%)		1/408 (0.2%)
Thoracic vertebral fracture	1/404 (0.2%)		0/408 (0%)
Investigations
Blood amylase increased	0/404 (0%)		1/408 (0.2%)
Lipase increased	0/404 (0%)		1/408 (0.2%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/404 (0.2%)		2/408 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma	0/404 (0%)		1/408 (0.2%)
Nervous system disorders
Convulsion	0/404 (0%)		2/408 (0.5%)
Transient ischaemic attack	2/404 (0.5%)		0/408 (0%)
Cerebral infarction	0/404 (0%)		1/408 (0.2%)
Ischaemic stroke	1/404 (0.2%)		0/408 (0%)
Presyncope	0/404 (0%)		1/408 (0.2%)
Psychiatric disorders
Anxiety	0/404 (0%)		1/408 (0.2%)
Renal and urinary disorders
Renal colic	1/404 (0.2%)		0/408 (0%)
Renal failure acute	1/404 (0.2%)		0/408 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/404 (0%)		1/408 (0.2%)
Pneumonia aspiration	0/404 (0%)		1/408 (0.2%)
Pulmonary oedema	0/404 (0%)		1/408 (0.2%)
Vascular disorders
Arteriosclerosis	1/404 (0.2%)		1/408 (0.2%)
Other (Not Including Serious) Adverse Events
	Albiglutide 50 mg		Liraglutide 1.8 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	266/404 (65.8%)		289/408 (70.8%)
Blood and lymphatic system disorders
Anaemia	5/404 (1.2%)		10/408 (2.5%)
Gastrointestinal disorders
Diarrhoea	60/404 (14.9%)		55/408 (13.5%)
Nausea	40/404 (9.9%)		119/408 (29.2%)
Vomiting	20/404 (5%)		38/408 (9.3%)
Constipation	17/404 (4.2%)		25/408 (6.1%)
Dyspepsia	17/404 (4.2%)		25/408 (6.1%)
Abdominal pain upper	11/404 (2.7%)		10/408 (2.5%)
Abdominal distension	11/404 (2.7%)		8/408 (2%)
Abdominal pain	10/404 (2.5%)		11/408 (2.7%)
Flatulence	10/404 (2.5%)		9/408 (2.2%)
Gastrooesophageal reflux disease	9/404 (2.2%)		14/408 (3.4%)
General disorders
Injection site reaction	28/404 (6.9%)		5/408 (1.2%)
Fatigue	13/404 (3.2%)		10/408 (2.5%)
Injection site haematoma	7/404 (1.7%)		9/408 (2.2%)
Oedema peripheral	4/404 (1%)		10/408 (2.5%)
Infections and infestations
Upper respiratory tract infection	42/404 (10.4%)		45/408 (11%)
Urinary tract infection	25/404 (6.2%)		23/408 (5.6%)
Nasopharyngitis	24/404 (5.9%)		28/408 (6.9%)
Sinusitis	12/404 (3%)		7/408 (1.7%)
Bronchitis	11/404 (2.7%)		9/408 (2.2%)
Influenza	7/404 (1.7%)		13/408 (3.2%)
Gastroenteritis	7/404 (1.7%)		11/408 (2.7%)
Injury, poisoning and procedural complications
Contusion	5/404 (1.2%)		9/408 (2.2%)
Investigations
Lipase increased	22/404 (5.4%)		28/408 (6.9%)
Metabolism and nutrition disorders
Hypoglycaemia	66/404 (16.3%)		83/408 (20.3%)
Decreased appetite	12/404 (3%)		28/408 (6.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	16/404 (4%)		12/408 (2.9%)
Back pain	15/404 (3.7%)		19/408 (4.7%)
Nervous system disorders
Headache	22/404 (5.4%)		22/408 (5.4%)
Dizziness	10/404 (2.5%)		21/408 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	10/404 (2.5%)		12/408 (2.9%)
Vascular disorders
Hypertension	13/404 (3.2%)		15/408 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.