Phase 3 28-Week Study With 24-Week and 52-week Extension Phases to Evaluate Efficacy and Safety of Exenatide Once Weekly and Dapagliflozin Versus Exenatide and Dapagliflozin Matching Placebo

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02229396
• Collaborator: (none)
• Enrollment: 695
• Locations: 134
• Arms: 3
• Actual Duration (Months): 39.8
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Study D5553C0003 is a 28-week, randomized, double-blind, active-controlled, multicenter, Phase 3 efficacy and safety study with 24-week and 52-week extension phases of simultaneous administration of exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg once daily (QD) compared to EQW 2 mg alone and dapagliflozin 10 mg QD alone in patients with Type 2 diabetes who have inadequate glycemic control on metformin.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Drug: Exantide with Dapagliflozin; Drug: Exentide; Drug: Dapagliflozin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 695 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 28-week, Multicenter, Randomized, Double-Blind, Active-Controlled, Phase 3 Study With a 24-week Extension Phase Followed by a 52-week Extension Phase to Evaluate the Efficacy and Safety of Simultaneous Administration of Exenatide Once Weekly 2 mg and Dapagliflozin Once Daily 10 mg Compared to Exenatide Once Weekly 2 mg Alone and Dapagliflozin Once Daily 10 mg Alone in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin
• Actual Study Start Date: Sep 4, 2014
• Actual Primary Completion Date: Apr 26, 2016
• Actual Study Completion Date: Dec 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide Once Weekly 2 mg and Dapagliflozin Once Daily 10 mg	Drug: Exantide with Dapagliflozin; 2 mg weekly suspension injection and 10 mg Dapagliflozin
Experimental: Exenatide Once Weekly 2 mg Alone	Drug: Exentide; 2 mg
Active Comparator: Dapagliflozin Once Daily 10 mg Alone	Drug: Dapagliflozin; 10 mg once daily Dapagliflozin

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c From Baseline to Week 28 [Baseline to Week 28]

   To compare the change from baseline to Week 28 in HbA1c between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.

Secondary Outcome Measures

1. Change in Body Weight From Baseline to Week 28 [Baseline to Week 28]

   To compare the change from baseline to Week 28 in body weight between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.

2. Change in Fasting Plasma Glucose From Baseline to Week 28 [Baseline to Week 28]

   To compare the change from baseline to Week 28 in fasting plasma glucose between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.

3. Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test [Baseline to Week 28]

   To compare the change from baseline to Week 28 in 2-hour postprandial glucose after a standard Meal Tolerance Test between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.

4. Percentage of Patients Achieving Weight Loss ≥5.0% at Week 28 [Baseline to Week 28]

   To compare the percentage of patients achieving weight loss ≥5.0% at 28 weeks between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.

5. Change in Fasting Plasma Glucose From Baseline to Week 2 [Baseline to Week 2]

   To compare the change from baseline to Week 2 in fasting plasma glucose between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.

6. Percentage of Patients Achieving HbA1c <7% at Week 28 [Baseline to Week 28]

   To compare the percentage of patients achieving HbA1c <7% at 28 weeks between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.

7. Change in Systolic Blood Pressure From Baseline to Week 28 [Baseline to Week 28]

   To compare the change from baseline to Week 28 in systolic blood pressure between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

• Has a diagnosis of T2DM.

• Has HbA1c of 8.0% to 12.0%, inclusive, at Visit 1 and Visit 2.

• Treated with a stable dose of metformin ≥1500 mg/day for at least 2 months prior to Screening.

Exclusion criteria

• FPG ≥280 mg/dL (15.6 mmol/L).

• Serum calcitonin concentration ≥40 pg/mL (≥40 ng/L) at Visit 1 (Screening)

• Clinically significant abnormal free T4 values or patients needing initiation or adjustment of thyroid treatment according to the investigator.

• Abnormal thyroid stimulating hormone (TSH) value at Screening will be further evaluated by free T4.Patients with clinically significant abnormal free T4 values will be excluded.

• Known active proliferative retinopathy.

• History of, or currently have, acute or chronic pancreatitis, or have triglyceride concentrations ≥500 mg/dL (≥5.65 mmol/L) at Visit 1

• History or presence of inflammatory bowel disease or other severe GI diseases, particularly those which may impact gastric emptying, such as gastroparesis or pyloric stenosis.

• History of gastric bypass surgery or gastric banding surgery, or either procedure is planned during the time period of the study. Current use of gastric balloons is also excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35235
2	Research Site	Huntsville	Alabama	United States	35801
3	Research Site	Tuscumbia	Alabama	United States	35674
4	Research Site	Glendale	Arizona	United States	85306
5	Research Site	Tempe	Arizona	United States	85283
6	Research Site	Anaheim	California	United States	92801
7	Research Site	Chula Vista	California	United States	91911
8	Research Site	El Cajon	California	United States	92020
9	Research Site	Fresno	California	United States	93720
10	Research Site	La Mesa	California	United States	91942
11	Research Site	Long Beach	California	United States	90807
12	Research Site	Los Angeles	California	United States	90057
13	Research Site	Mission Hills	California	United States	91345
14	Research Site	Montclair	California	United States	91763
15	Research Site	Oceanside	California	United States	92056
16	Research Site	San Diego	California	United States	92103
17	Research Site	San Diego	California	United States	92114
18	Research Site	Tustin	California	United States	92780
19	Research Site	Van Nuys	California	United States	91405
20	Research Site	Boynton Beach	Florida	United States	33437
21	Research Site	Clearwater	Florida	United States	33765
22	Research Site	Coral Gables	Florida	United States	33134
23	Research Site	Fort Lauderdale	Florida	United States	33316
24	Research Site	Hialeah	Florida	United States	33012
25	Research Site	Jacksonville	Florida	United States	32256
26	Research Site	Jacksonville	Florida	United States	32277
27	Research Site	Miami	Florida	United States	33126
28	Research Site	Miami	Florida	United States	33133
29	Research Site	Miami	Florida	United States	33135
30	Research Site	Miami	Florida	United States	33142
31	Research Site	Miami	Florida	United States	33165
32	Research Site	Miami	Florida	United States	33175
33	Research Site	Miami	Florida	United States	33186
34	Research Site	North Miami Beach	Florida	United States	33162
35	Research Site	Orlando	Florida	United States	32801
36	Research Site	Orlando	Florida	United States	32806
37	Research Site	Tampa	Florida	United States	33603
38	Research Site	Williston	Florida	United States	32696
39	Research Site	Chicago	Illinois	United States	60607
40	Research Site	Avon	Indiana	United States	46123
41	Research Site	Evansville	Indiana	United States	47714
42	Research Site	Franklin	Indiana	United States	46131
43	Research Site	Muncie	Indiana	United States	47304
44	Research Site	Newton	Kansas	United States	67114
45	Research Site	Monroe	Louisiana	United States	71201
46	Research Site	Hazelwood	Missouri	United States	63042
47	Research Site	Bellevue	Nebraska	United States	68005
48	Research Site	Las Vegas	Nevada	United States	89109
49	Research Site	Haddon Heights	New Jersey	United States	08035
50	Research Site	Burlington	North Carolina	United States	27215
51	Research Site	Greensboro	North Carolina	United States	27408
52	Research Site	Mooresville	North Carolina	United States	28117
53	Research Site	Morehead City	North Carolina	United States	28557
54	Research Site	Cincinnati	Ohio	United States	45242
55	Research Site	Vandalia	Ohio	United States	45377
56	Research Site	Medford	Oregon	United States	97504
57	Research Site	Philadelphia	Pennsylvania	United States	91307
58	Research Site	Charleston	South Carolina	United States	29407
59	Research Site	Greer	South Carolina	United States	29651
60	Research Site	Spartanburg	South Carolina	United States	29303
61	Research Site	Summerville	South Carolina	United States	29485
62	Research Site	Dakota Dunes	South Dakota	United States	57049
63	Research Site	Memphis	Tennessee	United States	38119
64	Research Site	Dallas	Texas	United States	75218
65	Research Site	Dallas	Texas	United States	75230
66	Research Site	Houston	Texas	United States	77074
67	Research Site	Houston	Texas	United States	77079
68	Research Site	Houston	Texas	United States	77090
69	Research Site	Pearland	Texas	United States	77584
70	Research Site	San Antonio	Texas	United States	78229
71	Research Site	Tomball	Texas	United States	77375
72	Research Site	Clinton	Utah	United States	84015
73	Research Site	Salt Lake City	Utah	United States	84102
74	Research Site	Burke	Virginia	United States	22015
75	Research Site	Manassas	Virginia	United States	20110
76	Research Site	Richmond	Virginia	United States	23294
77	Research Site	Baja		Hungary	6500
78	Research Site	Balatonfüred		Hungary	8230
79	Research Site	Budapest		Hungary	1033
80	Research Site	Budapest		Hungary	1083
81	Research Site	Budapest		Hungary	1088
82	Research Site	Budaörs		Hungary	2040
83	Research Site	Debrecen		Hungary	4025
84	Research Site	Eger		Hungary	3300
85	Research Site	Godollo		Hungary	2100
86	Research Site	Gyula		Hungary	5700
87	Research Site	Gödöllő		Hungary	2100
88	Research Site	Kecskemét		Hungary	6000
89	Research Site	Komárom		Hungary	2921
90	Research Site	Létavértes		Hungary	4281
91	Research Site	Nyíregyháza		Hungary	4405
92	Research Site	Pécs		Hungary	7623
93	Research Site	Szeged		Hungary	6722
94	Research Site	Szekszárd		Hungary	7100
95	Research Site	Lodz		Poland	94-255
96	Research Site	Lublin		Poland	20-538
97	Research Site	Oświęcim		Poland	32-600
98	Research Site	Parczew		Poland	21-200
99	Research Site	Poznań		Poland	61-655
100	Research Site	Torun		Poland	87-100
101	Research Site	Zgierz		Poland	95-100
102	Research Site	Łódź		Poland	94-048
103	Research Site	Baia Mare		Romania	430222
104	Research Site	Bucuresti		Romania	010192
105	Research Site	Bucuresti		Romania	010825
106	Research Site	Bucuresti		Romania	020475
107	Research Site	Galati		Romania	800578
108	Research Site	Oradea		Romania	410032
109	Research Site	Oradea		Romania	410169
110	Research Site	Oradea		Romania	410469
111	Research Site	Ploiesti		Romania	100342
112	Research Site	Timișoara		Romania	300456
113	Research Site	Banska Bystrica		Slovakia	97517
114	Research Site	Bardejov		Slovakia	085 01
115	Research Site	Bratislava		Slovakia	81108
116	Research Site	Bratislava		Slovakia	82106
117	Research Site	Bratislava		Slovakia	85101
118	Research Site	Dolny Kubin		Slovakia	026 01
119	Research Site	Kosice		Slovakia	04001
120	Research Site	Levice		Slovakia	934 01
121	Research Site	Levice		Slovakia	93401
122	Research Site	Lucenec		Slovakia	984 01
123	Research Site	Nitra		Slovakia	94911
124	Research Site	Pezinok		Slovakia	90201
125	Research Site	Sturovo		Slovakia	943 01
126	Research Site	Trebišov		Slovakia	07501
127	Research Site	Bloemfontein		South Africa	9301
128	Research Site	Cape Town		South Africa	7925
129	Research Site	Johannesburg		South Africa	1818
130	Research Site	Kempton Park		South Africa	1619
131	Research Site	Middelburg		South Africa	1055
132	Research Site	Parow		South Africa	7505
133	Research Site	Port Elizabeth		South Africa	6014
134	Research Site	Pretoria		South Africa	0001

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CSP_radacted

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02229396
• Other Study ID Numbers: D5553C00003; 2014-003503-29
• First Posted: Sep 1, 2014
• Last Update Posted: Dec 31, 2018
• Last Verified: Dec 1, 2018

• Keywords provided by AstraZeneca: Diabetes Mellitus; Exenatide; Dapagliflozin; Diabetes medication; Treatment efficacy; Placebo; Metabolism; Cardiovascular metabolic
• Additional relevant MeSH terms: Diabetes Mellitus; Dapagliflozin

Study Results

Participant Flow

Recruitment Details	Study conducted between 04 September 2014 and 28 December 2017. 118 centers in 6 countries randomized patients in the study. A Primary Analysis was performed following completion of the 28-week Treatment Period with a data cut-off date of 26 April 2016. All Primary and Secondary Outcome measures were reported at the time of the Primary Analysis.
Pre-assignment Detail	The study had a Screening Visit, a 1-week placebo Lead-in Period, a Randomization Visit, and 9 further visits at 1- to 4-week intervals during a 28-week Treatment Period. Patients then entered a 24-week Extension Period 1 and subsequent 52-week Extension Period 2. A follow-up visit occurred 10 weeks after last dose of study medication.

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 milligram (mg) tablet administered orally once daily + matching placebo for exenatide administered as subcutaneous (SC) injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Period Title: Overall Study
STARTED	233	231	231
Randomization Code Allocated	233	231	231
Safety Analysis Set	233	231	230
Intent-to-Treat (ITT) Analysis Set	230	228	227
Completed 28-Week Study Period	208	202	193
Completed 52-Week Study Period	194	193	177
COMPLETED	155	154	136
NOT COMPLETED	78	77	95

Baseline Characteristics

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo	Total
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Total of all reporting groups
Overall Participants	230	228	227	685
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.5 (9.16)	53.8 (9.82)	54.2 (9.62)	54.2 (9.53)
Sex: Female, Male (Count of Participants)
Female	120 52.2%	126 55.3%	111 48.9%	357 52.1%
Male	110 47.8%	102 44.7%	116 51.1%	328 47.9%
Race/Ethnicity, Customized (Number) [Number]
American Indian Or Alaska Native	0 0%	0 0%	2 0.9%	2 0.3%
Asian	1 0.4%	3 1.3%	1 0.4%	5 0.7%
Black Or African American	33 14.3%	34 14.9%	27 11.9%	94 13.7%
Other	7 3%	1 0.4%	3 1.3%	11 1.6%
White	189 82.2%	190 83.3%	194 85.5%	573 83.6%

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c From Baseline to Week 28
Description	To compare the change from baseline to Week 28 in HbA1c between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Measure Participants	230	228	227
Least Squares Mean (95% Confidence Interval) [% HbA1c]	-1.39	-1.98	-1.60

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide + Dapagliflozin, Exenatide + Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.63 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.129
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin + Placebo, Exenatide + Dapagliflozin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -0.84 to -0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.127
	Estimation Comments

2. Secondary Outcome

Title	Change in Body Weight From Baseline to Week 28
Description	To compare the change from baseline to Week 28 in body weight between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Measure Participants	230	228	227
Least Squares Mean (95% Confidence Interval) [kilogram]	-2.22	-3.55	-1.56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide + Dapagliflozin, Exenatide + Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95%; -2.79 to -1.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.406
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin + Placebo, Exenatide + Dapagliflozin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.33
	Confidence Interval	(2-Sided) 95%; -2.12 to -0.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.400
	Estimation Comments

3. Secondary Outcome

Title	Change in Fasting Plasma Glucose From Baseline to Week 28
Description	To compare the change from baseline to Week 28 in fasting plasma glucose between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Measure Participants	230	228	227
Least Squares Mean (95% Confidence Interval) [milligrams/deciliter (mg/dL)]	-49.19	-65.83	-45.75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide + Dapagliflozin, Exenatide + Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-20.08
	Confidence Interval	(2-Sided) 95%; -27.95 to -12.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.007
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin + Placebo, Exenatide + Dapagliflozin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.64
	Confidence Interval	(2-Sided) 95%; -24.39 to -8.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.947
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test
Description	To compare the change from baseline to Week 28 in 2-hour postprandial glucose after a standard Meal Tolerance Test between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Measure Participants	230	228	227
Least Squares Mean (95% Confidence Interval) [mg/dL]	-61.05	-87.83	-60.09

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide + Dapagliflozin, Exenatide + Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Treatment, region, and baseline HbA1c stratum (<9.0% or ≥9.0%), as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-27.74
	Confidence Interval	(2-Sided) 95%; -37.89 to -17.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.168
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin + Placebo, Exenatide + Dapagliflozin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	Treatment, region, and baseline HbA1c stratum (<9.0% or ≥9.0%), as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-26.78
	Confidence Interval	(2-Sided) 95%; -36.78 to -16.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.090
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Patients Achieving Weight Loss ≥5.0% at Week 28
Description	To compare the percentage of patients achieving weight loss ≥5.0% at 28 weeks between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Measure Participants	230	228	227
Number (95% Confidence Interval) [% of patients]	20.0	33.3	13.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide + Dapagliflozin, Exenatide + Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline HbA1c (<9.0% or ≥9.0%).
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	19.7
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin + Placebo, Exenatide + Dapagliflozin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline HbA1c (<9.0% or ≥9.0%).
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	13.3
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change in Fasting Plasma Glucose From Baseline to Week 2
Description	To compare the change from baseline to Week 2 in fasting plasma glucose between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame	Baseline to Week 2

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Measure Participants	230	228	227
Least Squares Mean (95% Confidence Interval) [mg/dL]	-26.31	-41.34	-21.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide + Dapagliflozin, Exenatide + Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-20.26
	Confidence Interval	(2-Sided) 95%; -27.12 to -13.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.494
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin + Placebo, Exenatide + Dapagliflozin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	This is a nominal p-value.
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.03
	Confidence Interval	(2-Sided) 95%; -21.85 to -8.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.477
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Patients Achieving HbA1c <7% at Week 28
Description	To compare the percentage of patients achieving HbA1c <7% at 28 weeks between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Measure Participants	230	228	227
Number (95% Confidence Interval) [% of patients]	19.1	44.7	26.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide + Dapagliflozin, Exenatide + Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline HbA1c (<9.0% or ≥9.0%).
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	17.9
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin + Placebo, Exenatide + Dapagliflozin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline HbA1c (<9.0% or ≥9.0%).
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	25.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change in Systolic Blood Pressure From Baseline to Week 28
Description	To compare the change from baseline to Week 28 in systolic blood pressure between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline HbA1c assessment.

Arm/Group Title	Dapagliflozin + Placebo	Exenatide + Dapagliflozin	Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.	Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
Measure Participants	230	228	227
Least Squares Mean (95% Confidence Interval) [millimeters of mercury (mmHg)]	-1.8	-4.3	-1.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide + Dapagliflozin, Exenatide + Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.0
	Confidence Interval	(2-Sided) 95%; -5.2 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin + Placebo, Exenatide + Dapagliflozin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment, region, baseline HbA1c stratum (<9.0% or ≥9.0%), week, and treatment by week interaction as fixed factors; baseline value as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -4.5 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.06
	Estimation Comments

Adverse Events

Time Frame	From baseline (Day 1) up to Week 104 (28-week Treatment Period + 24-week Extension Period 1 + 52-week Extension Period 2).
Adverse Event Reporting Description	Treatment-emergent adverse event data is reported for the Safety Analysis set defined as all randomized patients receiving at least 1 dose of study medication. One patient who was randomized did not receive study medication (the patient was randomized in error); this patient was not counted as completing or discontinuing treatment.
Arm/Group Title	Dapagliflozin + Placebo		Exenatide + Dapagliflozin		Exenatide + Placebo
Arm/Group Description	Dapagliflozin 10 mg tablet administered orally once daily + matching placebo for exenatide administered as SC injection once weekly. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.		Exenatide once weekly (EQW) 2 mg administered as SC injection + dapagliflozin 10 mg tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.		Exenatide once weekly (EQW) 2 mg administered as SC injection + matching placebo for dapagliflozin tablet administered orally once daily. Patients continued to administer the same type and dose of metformin therapy they were using at study entry.
All Cause Mortality
	Dapagliflozin + Placebo		Exenatide + Dapagliflozin		Exenatide + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/233 (0.9%)		3/231 (1.3%)		1/230 (0.4%)
Serious Adverse Events
	Dapagliflozin + Placebo		Exenatide + Dapagliflozin		Exenatide + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/233 (7.7%)		17/231 (7.4%)		18/230 (7.8%)
Cardiac disorders
Acute myocardial infarction	2/233 (0.9%)	2	0/231 (0%)	0	1/230 (0.4%)	1
Angina pectoris	0/233 (0%)	0	0/231 (0%)	0	1/230 (0.4%)	1
Arteriosclerosis coronary artery	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Atrial fibrillation	1/233 (0.4%)	1	0/231 (0%)	0	2/230 (0.9%)	2
Bradycardia	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Coronary artery occlusion	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Myocardial infarction	0/233 (0%)	0	0/231 (0%)	0	2/230 (0.9%)	2
Palpitations	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Tachycardia	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Ear and labyrinth disorders
Tinnitus	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Endocrine disorders
Pituitary-dependent Cushing's syndrome	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Gastrointestinal disorders
Abdominal pain lower	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Anal haemorrhage	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Colitis	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Gastritis	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Gastrooesophageal reflux disease	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Pancreatic necrosis	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Umbilical hernia	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
General disorders
Chest pain	1/233 (0.4%)	1	0/231 (0%)	0	1/230 (0.4%)	1
Non-cardiac chest pain	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Hepatobiliary disorders
Biliary dyskinesia	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Cholecystitis	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Cholelithiasis	0/233 (0%)	0	2/231 (0.9%)	2	1/230 (0.4%)	1
Immune system disorders
Anaphylactic reaction	1/233 (0.4%)	1	0/231 (0%)	0	1/230 (0.4%)	1
Infections and infestations
Cellulitis	0/233 (0%)	0	0/231 (0%)	0	1/230 (0.4%)	2
Diverticulitis	0/233 (0%)	0	0/231 (0%)	0	1/230 (0.4%)	1
Meningitis viral	0/233 (0%)	0	0/231 (0%)	0	1/230 (0.4%)	1
Osteomyelitis	1/233 (0.4%)	2	0/231 (0%)	0	0/230 (0%)	0
Pneumonia	0/233 (0%)	0	1/231 (0.4%)	1	1/230 (0.4%)	1
Injury, poisoning and procedural complications
Rib fracture	0/233 (0%)	0	0/231 (0%)	0	1/230 (0.4%)	1
Splenic rupture	0/233 (0%)	0	0/231 (0%)	0	1/230 (0.4%)	1
Multiple injuries	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Spinal compression fracture	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Toxicity to various agents	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Investigations
Hepatic enzyme increased	0/233 (0%)	0	0/231 (0%)	0	2/230 (0.9%)	2
Metabolism and nutrition disorders
Hyperglycaemia	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Hypoglycaemia	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Musculoskeletal and connective tissue disorders
Exostosis	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Intervertebral disc protrusion	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Osteoarthritis	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Periarthritis	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Lipoma	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Pancreatic carcinoma	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Renal neoplasm	0/233 (0%)	0	0/231 (0%)	0	1/230 (0.4%)	1
Nervous system disorders
Diabetic neuropathy	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Haemorrhagic stroke	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Ischaemic stroke	1/233 (0.4%)	1	0/231 (0%)	0	1/230 (0.4%)	1
Optic neuritis	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Presyncope	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Transient ischaemic attack	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Psychiatric disorders
Anxiety	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Suicidal ideation	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Renal and urinary disorders
Hydronephrosis	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/233 (0.4%)	2	0/231 (0%)	0	0/230 (0%)	0
Interstitial lung disease	0/233 (0%)	0	0/231 (0%)	0	1/230 (0.4%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Vascular disorders
Hypertension	1/233 (0.4%)	1	0/231 (0%)	0	0/230 (0%)	0
Hypotension	0/233 (0%)	0	1/231 (0.4%)	1	0/230 (0%)	0
Other (Not Including Serious) Adverse Events
	Dapagliflozin + Placebo		Exenatide + Dapagliflozin		Exenatide + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/233 (31.3%)		87/231 (37.7%)		78/230 (33.9%)
Gastrointestinal disorders
Diarrhoea	11/233 (4.7%)	14	13/231 (5.6%)	17	17/230 (7.4%)	25
Nausea	10/233 (4.3%)	12	13/231 (5.6%)	14	26/230 (11.3%)	29
Vomiting	7/233 (3%)	7	8/231 (3.5%)	10	12/230 (5.2%)	15
General disorders
Injection site nodule	13/233 (5.6%)	22	20/231 (8.7%)	40	14/230 (6.1%)	24
Infections and infestations
Nasopharyngitis	12/233 (5.2%)	15	15/231 (6.5%)	17	8/230 (3.5%)	10
Upper respiratory tract infection	22/233 (9.4%)	25	15/231 (6.5%)	22	17/230 (7.4%)	29
Urinary tract infection	16/233 (6.9%)	23	19/231 (8.2%)	31	15/230 (6.5%)	24
Nervous system disorders
Headache	12/233 (5.2%)	12	16/231 (6.9%)	18	12/230 (5.2%)	12

Limitations/Caveats

[Not Specified]

More Information

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

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