A Study of LY2189265 in Japanese Participants With Type 2 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01558271
• Collaborator: (none)
• Enrollment: 492
• Locations: 14
• Arms: 3
• Duration (Months): 26
• Patients Per Site: 35.1
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this trial is to examine the efficacy and safety of once-weekly LY2189265 in participants with type 2 diabetes mellitus who are not taking oral antidiabetic medication.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: LY2189265; Drug: Placebo; Drug: Liraglutide	Phase 3

Detailed Description

Rescue therapy (defined as alternative antihyperglycemic medication use or dose modification of oral antihyperglycemic medication [OAM]) may have been initiated during the planned treatment period if the participant discontinued study drug or met prespecified thresholds for severe, persistent hyperglycemia. Efficacy data, as well as data for hypoglycemic episodes from participants who permanently discontinued study treatment but switched to another diabetes medication and remained in the study, were censored from the point of initiating new treatment onwards.

Study Design

• Study Type: Interventional
• Actual Enrollment: 492 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study of LY2189265 Monotherapy Compared to Placebo and Liraglutide in Patients With Type 2 Diabetes Mellitus
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2189265 Once-weekly subcutaneous (SC) injection of 0.75 milligrams (mg) of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Drug: LY2189265; Other Names: Dulaglutide
Placebo Comparator: Placebo/LY2189265 Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Drug: LY2189265; Other Names: Dulaglutide ; Drug: Placebo
Active Comparator: Liraglutide Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.	Drug: Liraglutide

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks [Baseline, 26 weeks]

   Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, prestudy therapy (oral antihyperglycemic medication [OAM] yes/no), baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect.

Secondary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 52 Weeks [Baseline, 52 weeks]

   LS means were calculated using MMRM analysis with treatment, visit, treatment-by-visit, prestudy therapy (OAM yes/no), baseline BMI group (<25 or >=25 kg/m^2) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect.

2. Percentage of Participants Who Achieved HbA1c <=6.5% or <7% [Up to 26 and 52 weeks]

   The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% at Week 26 and Week 52 was analyzed with a Cochran-Mantel-Haenszel test stratified by prestudy therapy (OAM yes/no) and baseline BMI group (<25 or >=25 kg/m^2).

3. Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

   LS means were calculated using MMRM analysis with treatment, visit, treatment-by-visit, prestudy therapy (OAM yes/no), baseline BMI group (<25 or >=25 kg/m^2) as fixed effects, baseline FBG as a covariate, and participant as a random effect.

4. Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

   Participants were to test and record SMBG concentrations in their study diaries before each meal (breakfast, lunch, and dinner), approximately 2 hours after the start of each meal, and at bedtime. LS means were calculated using analysis of covariance (ANCOVA) model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline SMBG as a covariate.

5. Change From Baseline in Body Weight at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

   LS means were calculated using MMRM analysis with treatment, visit, treatment-by-visit, prestudy therapy (OAM yes/no), baseline BMI group (<25 or >=25 kg/m^2) as fixed effects, baseline body weight as a covariate, and participant as a random effect.

6. Change From Baseline in Insulin Sensitivity Using Updated Homeostasis Model Assessment (HOMA 2) at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

   HOMA 2 quantifies insulin resistance and beta-cell function. HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. Change in insulin sensitivity was assessed based on change from baseline of HOMA2-%S using fasting insulin (FI) and fasting C-peptide (FCP). LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline HOMA2-%S as a covariate.

7. Change From Baseline in Beta-cell Function Using Updated Homeostasis Model Assessment (HOMA 2) at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

   HOMA 2 quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta-cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. Change in beta-cell function was assessed based on change from baseline of HOMA2-%B using fasting insulin (FI) and fasting C-peptide (FCP). LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline HOMA2-%B as a covariate.

8. Percentage of Participants With Hypoglycemic Episodes [Baseline through 26 weeks and Baseline through 52 weeks]

   The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least one hypoglycemic episode over the 26-week or 52-week treatment period by the total number of participants analyzed, multiplied by 100%. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

9. 30-Day Rate of Hypoglycemic Episodes [Baseline through 26 weeks and Baseline through 52 weeks]

   The 30-day total hypoglycemia rate over 26 weeks and 52 weeks of treatment is summarized. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

10. Number of Participants With Adjudicated Cardiovascular Events at 26 Weeks and 52 Weeks [Baseline through 26 weeks and Baseline through 52 weeks]

    Deaths and nonfatal cardiovascular adverse events were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular events subjected to adjudication included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

11. Change From Baseline in Pulse Rate at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

    Sitting pulse rate was measured. LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline pulse rate as a covariate.

12. Change From Baseline in Blood Pressure at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

    Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline blood pressure as a covariate.

13. Number of Participants With Adjudicated Pancreatitis at 26 Weeks and 52 Weeks [Baseline through 26 weeks and Baseline through 52 weeks]

    Events of pancreatitis (including suspected pancreatitis and severe or serious abdominal pain) were adjudicated by a committee of expert physicians external to the Sponsor. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

14. Change From Baseline in Pancreatic Enzymes at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

    Pancreatic enzyme (lipase and total amylase) concentrations were measured.

15. Change From Baseline in Serum Calcitonin at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

16. Number of Participants With Treatment-Emergent LY2189265 Anti-Drug Antibodies (ADAs) at 26 Weeks and 52 Weeks [Baseline through 26 weeks and Baseline through 52 weeks]

    A participant was considered to have treatment-emergent LY2189265 ADAs if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from the baseline measurement.

17. Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26 Weeks and 52 Weeks [Baseline through 26 weeks and Baseline through 52 weeks]

    Additional intervention was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. The number of participants requiring additional intervention due to hyperglycemia is summarized cumulatively at 26 and 52 weeks.

18. Change From Baseline in Electrocardiogram Parameters at 26 Weeks and 52 Weeks [Baseline, 26 weeks, 52 weeks]

    Fridericia Corrected QT (QTcF) Interval and PR Interval are summarized. The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTcF = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. LS means were calculated using ANCOVA model with treatment as a fixed effect and the baseline ECG parameter as the covariate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants who have had a diagnosis of type 2 diabetes mellitus before screening.

• Participants who have been Oral Antihyperglycemic Medication (OAM)-naïve (diet and exercise only) or been taking OAM monotherapy except for thiazolidinedione (TZD) and are willing to discontinue this medication. Participants taking OAM monotherapy must complete 8-week washout period prior to randomization.

• Participants who are OAM naïve with a screening glycosylated hemoglobin (HbA1c) value of 7.0% to 10.0% and randomization HbA1c value of 7.0% to 10.0%, or who are taking OAM monotherapy with screening HbA1c value of 6.5% to 9.0% and randomization HbA1c value of 7.0% to 10.0%.

• Participants who have a body mass index (BMI) of 18.5 kilograms per meter squared (kg/m^{2) to 35.0 kg/m}2.

Exclusion Criteria:

• Participants who have a diagnosis of type 1 diabetes.

• Participants who have previously been treated with any other glucagon-like peptide-1 (GLP-1) analog.

• Participants who have been receiving more than half of the maximum dose of sulfonylureas at screening.

• Participants who have been currently taking insulin or TZD, or have had previous insulin or TZD treatment within 3 months before screening.

• Participants who have obvious clinical signs or symptoms of pancreatitis, a history of chronic pancreatitis or acute pancreatitis at screening, as determined by the investigator. Participants who have a serum amylase concentration ≥3 times the upper limit of the reference range and/or a serum lipase concentration ≥2 times the upper limit of the reference range, as determined by the central laboratory at screening.

• Participants who have self or family history of medullary C-cell hyperplasia, focal hyperplasia, or medullary thyroid carcinoma (MTC).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukuoka		Japan	819-0168
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hokkaido		Japan	060-8604
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hyogo		Japan	663-8501
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ibaraki		Japan	302-0118
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ishikawa		Japan	920-8641
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kanagawa		Japan	235-0045
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kumamoto		Japan	862-0976
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Miyagi		Japan	980-0021
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nagano		Japan	399-0006
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka		Japan	532-0003
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokyo		Japan	160-0022
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toyama		Japan	939-0363
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Yamaguchi		Japan	756-0095
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Yokohama		Japan	220-0012

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01558271
• Other Study ID Numbers: 13990; H9X-JE-GBDP
• First Posted: Mar 20, 2012
• Last Update Posted: May 22, 2015
• Last Verified: May 1, 2015

• Keywords provided by Eli Lilly and Company: GLP-1
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Liraglutide; Dulaglutide

Study Results

Participant Flow

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly subcutaneous (SC) injection of 0.75 milligrams (mg) of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Period Title: Overall Study
STARTED	281	70	141
Received at Least 1 Dose of Study Drug	280	70	137
Completed 26 Weeks	271	63	128
COMPLETED	263	59	124
NOT COMPLETED	18	11	17

Baseline Characteristics

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide	Total
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.	Total of all reporting groups
Overall Participants	280	70	137	487
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.15 (9.57)	57.66 (8.34)	57.91 (10.93)	57.44 (9.63)
Sex: Female, Male (Count of Participants)
Female	52 18.6%	15 21.4%	24 17.5%	91 18.7%
Male	228 81.4%	55 78.6%	113 82.5%	396 81.3%
Race/Ethnicity, Customized (participants) [Number]
Asian	280 100%	70 100%	137 100%	487 100%
Region of Enrollment (participants) [Number]
Japan	280 100%	70 100%	137 100%	487 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks
Description	Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, prestudy therapy (oral antihyperglycemic medication [OAM] yes/no), baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect.
Time Frame	Baseline, 26 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication with evaluable HbA1c data. Only pre-rescue measurements were used.

Arm/Group Title	LY2189265	Placebo	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 24 weeks of open therapy.
Measure Participants	280	68	136
Least Squares Mean (Standard Error) [percentage of HbA1c]	-1.43 (0.05)	0.14 (0.10)	-1.33 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments	Approximately 490 participants were to be randomized in a 4:1:2 ratio to LY2189265, placebo, or Liraglutide, respectively. This sample size would provide greater than 99% power to demonstrate superiority of LY2189265 to placebo. This computation assumed a true mean difference in HbA1c change from baseline between LY2189265 and placebo being 0.8%, a common standard deviation of 1.1%, a 1-sided significance level of 0.025, and a 9% drop-out rate between randomization and Week 26.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.57
	Confidence Interval	(2-Sided) 95%; -1.79 to -1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments	Approximately 490 participants were to be randomized in a 4:1:2 ratio to LY2189265, placebo, or Liraglutide, respectively. This sample size would provide >90% power to confirm non-inferiority of LY2189265 to liraglutide by a margin of 0.4%. This computation assumed a true mean difference in HbA1c change from baseline between LY2189265 and Liraglutide being 0%, a common standard deviation of 1.1%, a 1-sided significance level of 0.025, and a 9% drop-out rate between randomization and Week 26.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If the upper limit of the 95% Confidence Interval (CI) was <0.4%, then LY2189265 was declared non-inferior to Liraglutide. If the upper limit of the 95% CI was <0.0%, then LY2189265 was declared superior to liraglutide.
Statistical Test of Hypothesis	p-Value	0.248
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 52 Weeks
Description	LS means were calculated using MMRM analysis with treatment, visit, treatment-by-visit, prestudy therapy (OAM yes/no), baseline BMI group (<25 or >=25 kg/m^2) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect.
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication with evaluable HbA1c data. Only pre-rescue measurements were used.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	68	136
Least Squares Mean (Standard Error) [percentage of HbA1c]	-1.39 (0.06)	-1.55 (0.12)	-1.19 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.040
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.39 to -0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Who Achieved HbA1c <=6.5% or <7%
Description	The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% at Week 26 and Week 52 was analyzed with a Cochran-Mantel-Haenszel test stratified by prestudy therapy (OAM yes/no) and baseline BMI group (<25 or >=25 kg/m^2).
Time Frame	Up to 26 and 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least one dose of study medication with evaluable HbA1c data. Only pre-rescue measurements were used. Missing endpoints were imputed with the last observation carried forward (LOCF), using only postbaseline data.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	68	136
HbA1c <7%, 26 weeks	71.4 25.5%	5.9 8.4%	69.1 50.4%
HbA1c <=6.5%, 26 weeks	50.0 17.9%	1.5 2.1%	49.3 36%
HbA1c <7%, 52 weeks	67.9 24.3%	70.6 100.9%	60.3 44%
HbA1c <=6.5%, 52 weeks	49.3 17.6%	52.9 75.6%	41.2 30.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Treatment comparison for HbA1c <7% at 26 weeks between LY2189265 and placebo.
	Method	Cochran-Mantel-Haenszel
	Comments	Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.608
	Comments	Treatment comparison for HbA1c <7% at 26 weeks between LY2189265 and Liraglutide.
	Method	Cochran-Mantel-Haenszel
	Comments	Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Treatment comparison for HbA1c <=6.5% at 26 weeks between LY2189265 and placebo.
	Method	Cochran-Mantel-Haenszel
	Comments	Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.844
	Comments	Treatment comparison for HbA1c <=6.5% at 26 weeks between LY2189265 and Liraglutide.
	Method	Cochran-Mantel-Haenszel
	Comments	Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.112
	Comments	Treatment comparison for HbA1c <7% at 52 weeks between LY2189265 and Liraglutide.
	Method	Cochran-Mantel-Haenszel
	Comments	Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.103
	Comments	Treatment comparison for HbA1c <=6.5% at 52 weeks between LY2189265 and Liraglutide.
	Method	Cochran-Mantel-Haenszel
	Comments	Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.

4. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks
Description	LS means were calculated using MMRM analysis with treatment, visit, treatment-by-visit, prestudy therapy (OAM yes/no), baseline BMI group (<25 or >=25 kg/m^2) as fixed effects, baseline FBG as a covariate, and participant as a random effect.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least one dose of study medication with evaluable FBG data. Only pre-rescue measurements were used.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	276	62	134
26 weeks	-39.18 (1.60)	1.03 (3.30)	-39.75 (2.27)
52 weeks	-38.93 (1.72)	-40.93 (3.62)	-37.15 (2.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Treatment comparison for FBG at 26 weeks between LY2189265 and placebo.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-40.21
	Confidence Interval	(2-Sided) 95%; -47.31 to -33.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.835
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment comparison for FBG at 26 weeks between LY2189265 and Liraglutide.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; -4.82 to 5.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.553
	Comments	Treatment comparison for FBG at 52 weeks between LY2189265 and Liraglutide.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.77
	Confidence Interval	(2-Sided) 95%; -7.65 to 4.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) at 26 Weeks and 52 Weeks
Description	Participants were to test and record SMBG concentrations in their study diaries before each meal (breakfast, lunch, and dinner), approximately 2 hours after the start of each meal, and at bedtime. LS means were calculated using analysis of covariance (ANCOVA) model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline SMBG as a covariate.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication with evaluable SMBG data. Only pre-rescue measurements were used. Missing endpoints were imputed with the LOCF method, using only postbaseline data.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	277	69	133
Pre-morning meal, 26 weeks	-39.65 (1.55)	-0.15 (3.04)	-34.93 (2.19)
2 hours post-morning meal, 26 weeks	-69.64 (2.80)	-9.29 (5.48)	-61.67 (3.96)
Pre-midday meal, 26 weeks	-48.47 (2.05)	3.91 (4.03)	-45.08 (2.91)
2 hours post-midday meal, 26 weeks	-67.57 (2.94)	-1.50 (5.77)	-66.71 (4.16)
Pre-evening meal, 26 weeks	-39.64 (2.15)	9.25 (4.22)	-36.62 (3.05)
2 hours post-evening meal	-56.70 (2.83)	0.93 (5.56)	-53.14 (4.01)
Bedtime, 26 weeks	-53.39 (2.81)	4.26 (5.51)	-51.07 (3.94)
Pre-morning meal, 52 weeks	-37.46 (1.58)	-30.12 (3.10)	-33.41 (2.23)
2 hours post-morning meal, 52 weeks	-66.96 (2.87)	-65.91 (5.62)	-60.69 (4.06)
Pre-midday meal, 52 weeks	-47.03 (1.86)	-45.15 (3.64)	-46.25 (2.63)
2 hours post-midday meal, 52 weeks	-68.21 (2.74)	-58.52 (5.38)	-62.57 (3.88)
Pre-evening meal, 52 weeks	-41.04 (1.08)	-36.13 (3.70)	-32.86 (2.67)
2 hours post-evening meal, 52 weeks	-55.01 (2.58)	-55.26 (5.06)	-42.30 (3.65)
Bedtime, 52 weeks	-55.76 (2.39)	-51.19 (4.69)	-49.10 (3.35)

6. Secondary Outcome

Title	Change From Baseline in Body Weight at 26 Weeks and 52 Weeks
Description	LS means were calculated using MMRM analysis with treatment, visit, treatment-by-visit, prestudy therapy (OAM yes/no), baseline BMI group (<25 or >=25 kg/m^2) as fixed effects, baseline body weight as a covariate, and participant as a random effect.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication with evaluable body weight data. Only pre-rescue measurements were used.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	70	136
26 weeks	-0.02 (0.14)	-0.63 (0.29)	-0.36 (0.20)
52 weeks	-0.17 (0.18)	-1.03 (0.37)	-0.13 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.057
	Comments
	Method	Mixed Models Analysis
	Comments	Treatment comparison for body weight at 26 weeks between LY2189265 and placebo.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; -0.02 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.168
	Comments	Treatment comparison for body weight at 26 weeks between LY2189265 and Liraglutide.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.911
	Comments	Treatment comparison for body weight at 52 weeks between LY2189265 and Liraglutide.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.64 to 0.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Insulin Sensitivity Using Updated Homeostasis Model Assessment (HOMA 2) at 26 Weeks and 52 Weeks
Description	HOMA 2 quantifies insulin resistance and beta-cell function. HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. Change in insulin sensitivity was assessed based on change from baseline of HOMA2-%S using fasting insulin (FI) and fasting C-peptide (FCP). LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline HOMA2-%S as a covariate.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least one dose of study medication with evaluable HOMA2-%S data. Only pre-rescue measurements were used. Missing endpoints were imputed with the LOCF method, using only postbaseline data.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	275	62	131
HOMA2-%S based on FI, 26 weeks (n=254, 57, 115)	-4.83 (2.34)	-2.97 (4.83)	-4.82 (3.43)
HOMA2-%S based on FCP, 26 weeks (n=275, 62, 131)	-5.48 (1.93)	-6.32 (3.99)	-2.46 (2.75)
HOMA2-%S based on FI, 52 weeks (n=260, 60, 120)	-7.75 (2.34)	NA (NA)	-5.26 (3.38)
HOMA2-%S based on FCP, 52 weeks (n=275, 62, 131)	-11.72 (1.88)	NA (NA)	-10.68 (2.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.723
	Comments	Treatment comparison for HOMA2-%S based on fasting insulin at 26 weeks between LY2189265 and placebo.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.86
	Confidence Interval	(2-Sided) 95%; -12.20 to 8.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.998
	Comments	Treatment comparison for HOMA2-%S based on fasting insulin at 26 weeks between LY2189265 and Liraglutide.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -7.92 to 7.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.848
	Comments	Treatment comparison for HOMA2-%S based on fasting C-peptide at 26 weeks between LY2189265 and placebo.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; -7.72 to 9.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.357
	Comments	Treatment comparison for HOMA2-%S based on fasting C-peptide at 26 weeks between LY2189265 and Liraglutide.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.03
	Confidence Interval	(2-Sided) 95%; -9.48 to 3.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.533
	Comments	Treatment comparison for HOMA2-%S based on fasting insulin at 52 weeks between LY2189265 and Liraglutide.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.49
	Confidence Interval	(2-Sided) 95%; -10.35 to 5.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.747
	Comments	Treatment comparison for HOMA2-%S based on fasting C-peptide at 52 weeks between LY2189265 and Liraglutide.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.03
	Confidence Interval	(2-Sided) 95%; -7.32 to 5.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Beta-cell Function Using Updated Homeostasis Model Assessment (HOMA 2) at 26 Weeks and 52 Weeks
Description	HOMA 2 quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta-cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. Change in beta-cell function was assessed based on change from baseline of HOMA2-%B using fasting insulin (FI) and fasting C-peptide (FCP). LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline HOMA2-%B as a covariate.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least one dose of study medication with evaluable HOMA2-%B data. Only pre-rescue measurements were used. Missing endpoints were imputed with the LOCF method, using only postbaseline data.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	275	62	131
HHOMA2-%B based on FI, 26 weeks (n=254, 57, 115)	28.42 (1.54)	0.08 (3.14)	25.35 (2.23)
HOMA2-%B based on FCP, 26 weeks (n=275, 62, 131)	27.77 (1.27)	2.94 (2.61)	25.86 (1.79)
HOMA2-%B based on FI, 52 weeks (n=260, 60, 120)	27.81 (1.39)	NA (NA)	25.89 (1.99)
HOMA2-%B based on FCP, 52 weeks (n=275, 62, 131)	29.59 (1.37)	NA (NA)	28.85 (1.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Treatment comparison for HOMA2-%B based on fasting insulin at 26 weeks between LY2189265 and placebo.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	28.35
	Confidence Interval	(2-Sided) 95%; 21.63 to 35.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.242
	Comments	Treatment comparison for HOMA2-%B based on fasting insulin at 26 weeks between LY2189265 and Liraglutide.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.08
	Confidence Interval	(2-Sided) 95%; -2.09 to 8.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Treatment comparison for HOMA2-%B based on fasting C-peptide at 26 weeks between LY2189265 and placebo.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	24.82
	Confidence Interval	(2-Sided) 95%; 19.25 to 30.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.376
	Comments	Treatment comparison for HOMA2-%B based on fasting C-peptide at 26 weeks between LY2189265 and Liraglutide.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.91
	Confidence Interval	(2-Sided) 95%; -2.32 to 6.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.417
	Comments	Treatment comparison for HOMA2-%B based on fasting insulin at 52 weeks between LY2189265 and Liraglutide.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.91
	Confidence Interval	(2-Sided) 95%; -2.72 to 6.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.753
	Comments	Treatment comparison for HOMA2-%B based on fasting C-peptide at 52 weeks between LY2189265 and Liraglutide.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; -3.83 to 5.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With Hypoglycemic Episodes
Description	The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least one hypoglycemic episode over the 26-week or 52-week treatment period by the total number of participants analyzed, multiplied by 100%. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	70	137
26 weeks	2.1 0.8%	1.4 2%	1.5 1.1%
52 weeks	2.9 1%	2.9 4.1%	2.9 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments	Treatment comparison at 26 weeks between LY2189265 and placebo.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments	Treatment comparison at 26 weeks between LY2189265 and Liraglutide.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LY2189265, Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments	Treatment comparison at 52 weeks between LY2189265 and Liraglutide.
	Method	Fisher Exact
	Comments

10. Secondary Outcome

Title	30-Day Rate of Hypoglycemic Episodes
Description	The 30-day total hypoglycemia rate over 26 weeks and 52 weeks of treatment is summarized. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication. One participant in the Liraglutide reporting group received study drug but discontinued from the study on the same day and, therefore, was not included in the analysis.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	70	136
26 weeks	0.01 (0.04)	0.00 (0.02)	0.00 (0.02)
52 weeks	0.00 (0.02)	0.01 (0.09)	0.01 (0.04)

11. Secondary Outcome

Title	Number of Participants With Adjudicated Cardiovascular Events at 26 Weeks and 52 Weeks
Description	Deaths and nonfatal cardiovascular adverse events were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular events subjected to adjudication included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	70	137
26 weeks	0 0%	0 0%	0 0%
52 weeks	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	Change From Baseline in Pulse Rate at 26 Weeks and 52 Weeks
Description	Sitting pulse rate was measured. LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline pulse rate as a covariate.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least one dose of study medication with evaluable pulse rate data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	70	136
26 weeks	3.35 (0.45)	1.49 (0.90)	4.77 (0.64)
52 weeks	3.11 (0.42)	4.42 (0.86)	5.13 (0.60)

13. Secondary Outcome

Title	Change From Baseline in Blood Pressure at 26 Weeks and 52 Weeks
Description	Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline blood pressure as a covariate.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least one dose of study medication with evaluable blood pressure data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	70	136
SBP, 26 weeks	0.62 (0.62)	0.53 (1.25)	-2.10 (0.89)
DBP, 26 weeks	1.09 (0.39)	0.29 (0.78)	0.43 (0.56)
SBP, 52 weeks	1.32 (0.66)	0.37 (1.37)	-1.86 (0.95)
DBP, 52 weeks	1.41 (0.41)	1.16 (0.86)	1.17 (0.60)

14. Secondary Outcome

Title	Number of Participants With Adjudicated Pancreatitis at 26 Weeks and 52 Weeks
Description	Events of pancreatitis (including suspected pancreatitis and severe or serious abdominal pain) were adjudicated by a committee of expert physicians external to the Sponsor. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	70	137
26 weeks	0 0%	0 0%	0 0%
52 weeks	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Change From Baseline in Pancreatic Enzymes at 26 Weeks and 52 Weeks
Description	Pancreatic enzyme (lipase and total amylase) concentrations were measured.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least one dose of study medication with evaluable pancreatic enzyme data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	275	65	131
Lipase, 26 weeks	7.0	1.0	11.0
Total Amylase, 26 weeks	7.0	0.0	7.0
Lipase, 52 weeks	6.0	6.0	9.0
Total Amylase, 52 weeks	7.0	9.0	6.0

16. Secondary Outcome

Title	Change From Baseline in Serum Calcitonin at 26 Weeks and 52 Weeks
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least one dose of study medication with evaluable serum calcitonin data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	274	65	131
26 weeks	0.0	0.0	0.0
52 weeks	0.0	0.0	0.0

17. Secondary Outcome

Title	Number of Participants With Treatment-Emergent LY2189265 Anti-Drug Antibodies (ADAs) at 26 Weeks and 52 Weeks
Description	A participant was considered to have treatment-emergent LY2189265 ADAs if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from the baseline measurement.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication and had LY2189265 evaluable ADA data.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	279	68	134
26 weeks (n=279, 68, 133)	3 1.1%	0 0%	0 0%
52 weeks (n=279, 68, 134)	3 1.1%	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26 Weeks and 52 Weeks
Description	Additional intervention was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. The number of participants requiring additional intervention due to hyperglycemia is summarized cumulatively at 26 and 52 weeks.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study medication.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	280	70	137
26 weeks	0 0%	0 0%	0 0%
52 weeks	0 0%	0 0%	0 0%

19. Secondary Outcome

Title	Change From Baseline in Electrocardiogram Parameters at 26 Weeks and 52 Weeks
Description	Fridericia Corrected QT (QTcF) Interval and PR Interval are summarized. The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTcF = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. LS means were calculated using ANCOVA model with treatment as a fixed effect and the baseline ECG parameter as the covariate.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least one dose of study medication with evaluable ECG data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	LY2189265	Placebo/LY2189265	Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.	Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Measure Participants	274	65	128
QTcF, 26 weeks (n=273, 64, 128)	-2.02 (0.70)	-0.96 (1.44)	-1.89 (1.02)
QTcF, 52 weeks (n=274, 64, 128)	-2.76 (0.68)	-0.80 (1.41)	-4.35 (1.00)
PR, 26 weeks (n=269, 65, 126)	2.20 (0.60)	-0.45 (1.22)	2.07 (0.88)
PR, 52 weeks (n=270, 65, 126)	2.81 (0.82)	2.60 (1.33)	3.71 (1.03)

Adverse Events

Arm/Group Title	LY2189265		Placebo/LY2189265		Liraglutide
Arm/Group Description	Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.		Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.		Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
All Cause Mortality
	LY2189265		Placebo/LY2189265		Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2189265		Placebo/LY2189265		Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/280 (3.2%)		5/70 (7.1%)		7/137 (5.1%)
Blood and lymphatic system disorders
Eosinophilia	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Ear and labyrinth disorders
Sudden hearing loss	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Gastrointestinal disorders
Large intestine polyp	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Hepatobiliary disorders
Bile duct stone	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Infections and infestations
Bacterial infection	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Gastroenteritis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Hiv infection	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Pneumocystis jirovecii pneumonia	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Wound infection	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Injury, poisoning and procedural complications
Femoral neck fracture	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Hand fracture	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Lumbar spinal stenosis	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Rotator cuff syndrome	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Invasive ductal breast carcinoma	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Lung adenocarcinoma	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Ovarian cancer	0/52 (0%)	0	1/15 (6.7%)	1	0/24 (0%)	0
Pancreatic carcinoma	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Prostate cancer	0/228 (0%)	0	1/55 (1.8%)	1	0/113 (0%)	0
Nervous system disorders
Intracranial aneurysm	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Other (Not Including Serious) Adverse Events
	LY2189265		Placebo/LY2189265		Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	182/280 (65%)		53/70 (75.7%)		94/137 (68.6%)
Blood and lymphatic system disorders
Anaemia	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Anaemia macrocytic	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Cardiac disorders
Palpitations	5/280 (1.8%)	5	0/70 (0%)	0	0/137 (0%)	0
Ventricular extrasystoles	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Ear and labyrinth disorders
Deafness neurosensory	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Ear pain	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Eustachian tube obstruction	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Vertigo	2/280 (0.7%)	2	1/70 (1.4%)	1	1/137 (0.7%)	1
Endocrine disorders
Goitre	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Hyperthyroidism	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Eye disorders
Asthenopia	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Cataract	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Conjunctivitis allergic	0/280 (0%)	0	1/70 (1.4%)	2	1/137 (0.7%)	1
Diabetic retinopathy	2/280 (0.7%)	2	1/70 (1.4%)	1	2/137 (1.5%)	2
Dry eye	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Eyelid oedema	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Glaucoma	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Iritis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Keratitis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Macular oedema	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Pingueculitis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Retinal tear	1/280 (0.4%)	1	1/70 (1.4%)	1	1/137 (0.7%)	1
Vitreous floaters	1/280 (0.4%)	1	1/70 (1.4%)	1	0/137 (0%)	0
Vitreous haemorrhage	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	9/280 (3.2%)	10	1/70 (1.4%)	1	5/137 (3.6%)	5
Abdominal distension	12/280 (4.3%)	12	0/70 (0%)	0	7/137 (5.1%)	7
Abdominal pain	3/280 (1.1%)	3	2/70 (2.9%)	2	1/137 (0.7%)	1
Abdominal pain upper	4/280 (1.4%)	4	2/70 (2.9%)	2	3/137 (2.2%)	3
Abnormal faeces	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Anal fistula	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Constipation	22/280 (7.9%)	24	4/70 (5.7%)	4	11/137 (8%)	11
Dental caries	4/280 (1.4%)	5	3/70 (4.3%)	3	4/137 (2.9%)	4
Diarrhoea	20/280 (7.1%)	23	6/70 (8.6%)	6	6/137 (4.4%)	6
Diverticulum intestinal	0/280 (0%)	0	1/70 (1.4%)	1	1/137 (0.7%)	1
Dry mouth	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Dyschezia	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Dyspepsia	4/280 (1.4%)	5	1/70 (1.4%)	1	3/137 (2.2%)	3
Dysphagia	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Epigastric discomfort	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Eructation	2/280 (0.7%)	3	0/70 (0%)	0	0/137 (0%)	0
Flatulence	2/280 (0.7%)	2	0/70 (0%)	0	2/137 (1.5%)	2
Gastric disorder	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Gastric polyps	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Gastric ulcer	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Gastritis	2/280 (0.7%)	3	1/70 (1.4%)	1	3/137 (2.2%)	5
Gastritis atrophic	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Gastritis erosive	1/280 (0.4%)	1	1/70 (1.4%)	1	0/137 (0%)	0
Gastroduodenal ulcer	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Gastrooesophageal reflux disease	2/280 (0.7%)	2	1/70 (1.4%)	1	4/137 (2.9%)	4
Haemorrhoids	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Hiatus hernia	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Hyperchlorhydria	1/280 (0.4%)	3	0/70 (0%)	0	0/137 (0%)	0
Large intestine polyp	3/280 (1.1%)	3	0/70 (0%)	0	4/137 (2.9%)	4
Nausea	17/280 (6.1%)	25	2/70 (2.9%)	2	11/137 (8%)	18
Periodontal disease	1/280 (0.4%)	1	1/70 (1.4%)	1	0/137 (0%)	0
Radicular cyst	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Stomatitis	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Vomiting	5/280 (1.8%)	6	0/70 (0%)	0	1/137 (0.7%)	2
General disorders
Application site haematoma	1/280 (0.4%)	1	0/70 (0%)	0	2/137 (1.5%)	2
Chest pain	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Device failure	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Early satiety	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Fatigue	1/280 (0.4%)	1	0/70 (0%)	0	3/137 (2.2%)	3
Feeling abnormal	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Induration	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Injection site bruising	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Injection site dermatitis	1/280 (0.4%)	2	0/70 (0%)	0	0/137 (0%)	0
Injection site erythema	1/280 (0.4%)	1	0/70 (0%)	0	4/137 (2.9%)	5
Injection site haemorrhage	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Injection site induration	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Injection site pain	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Injection site pruritus	5/280 (1.8%)	5	0/70 (0%)	0	5/137 (3.6%)	6
Injection site rash	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Injection site reaction	3/280 (1.1%)	3	1/70 (1.4%)	1	0/137 (0%)	0
Injection site swelling	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Local swelling	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Malaise	2/280 (0.7%)	8	1/70 (1.4%)	1	1/137 (0.7%)	1
Oedema peripheral	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Pyrexia	1/280 (0.4%)	1	1/70 (1.4%)	1	0/137 (0%)	0
Thirst	0/280 (0%)	0	1/70 (1.4%)	1	1/137 (0.7%)	1
Xerosis	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Hepatobiliary disorders
Alcoholic liver disease	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Cholelithiasis	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Gallbladder polyp	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Hepatic cyst	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Hepatic function abnormal	1/280 (0.4%)	1	1/70 (1.4%)	1	1/137 (0.7%)	1
Hepatic steatosis	5/280 (1.8%)	5	0/70 (0%)	0	2/137 (1.5%)	2
Hyperplastic cholecystopathy	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Liver injury	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Immune system disorders
Seasonal allergy	2/280 (0.7%)	2	0/70 (0%)	0	1/137 (0.7%)	1
Infections and infestations
Acute sinusitis	1/280 (0.4%)	1	1/70 (1.4%)	1	0/137 (0%)	0
Anisakiasis	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Body tinea	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Bronchitis	7/280 (2.5%)	9	2/70 (2.9%)	2	3/137 (2.2%)	4
Bronchitis viral	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Candida infection	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Chronic sinusitis	1/280 (0.4%)	1	1/70 (1.4%)	1	1/137 (0.7%)	1
Conjunctivitis	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Cystitis	2/280 (0.7%)	3	1/70 (1.4%)	1	1/137 (0.7%)	1
Dermatitis infected	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Enteritis infectious	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Fungal skin infection	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Gastroenteritis	7/280 (2.5%)	7	0/70 (0%)	0	1/137 (0.7%)	1
Gastroenteritis viral	1/280 (0.4%)	1	1/70 (1.4%)	1	0/137 (0%)	0
Gingivitis	3/280 (1.1%)	3	0/70 (0%)	0	1/137 (0.7%)	1
Helicobacter gastritis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Helicobacter infection	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Herpes virus infection	0/280 (0%)	0	1/70 (1.4%)	1	1/137 (0.7%)	1
Herpes zoster	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Hordeolum	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Influenza	1/280 (0.4%)	1	3/70 (4.3%)	3	2/137 (1.5%)	2
Intervertebral discitis	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Nasopharyngitis	52/280 (18.6%)	61	7/70 (10%)	12	24/137 (17.5%)	34
Oral herpes	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Otitis externa	1/280 (0.4%)	1	1/70 (1.4%)	1	0/137 (0%)	0
Otitis media	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Parotitis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Periodontitis	1/280 (0.4%)	1	1/70 (1.4%)	1	1/137 (0.7%)	2
Pharyngitis	3/280 (1.1%)	3	3/70 (4.3%)	4	3/137 (2.2%)	3
Pharyngitis bacterial	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Pyoderma	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Rhinitis	3/280 (1.1%)	3	0/70 (0%)	0	0/137 (0%)	0
Sialoadenitis	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Sinusitis	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Tinea infection	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Tinea pedis	1/280 (0.4%)	1	1/70 (1.4%)	1	2/137 (1.5%)	2
Tooth abscess	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Upper respiratory tract infection	1/280 (0.4%)	2	1/70 (1.4%)	1	1/137 (0.7%)	1
Injury, poisoning and procedural complications
Arthropod bite	0/280 (0%)	0	1/70 (1.4%)	1	1/137 (0.7%)	3
Arthropod sting	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Chillblains	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Contusion	4/280 (1.4%)	4	0/70 (0%)	0	5/137 (3.6%)	5
Epicondylitis	0/280 (0%)	0	2/70 (2.9%)	2	1/137 (0.7%)	1
Excoriation	3/280 (1.1%)	3	0/70 (0%)	0	0/137 (0%)	0
Fibula fracture	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Hand fracture	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Laceration	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Ligament sprain	2/280 (0.7%)	3	0/70 (0%)	0	1/137 (0.7%)	1
Limb crushing injury	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Limb injury	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Meniscus injury	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Muscle strain	1/280 (0.4%)	1	0/70 (0%)	0	2/137 (1.5%)	2
Post-traumatic neck syndrome	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Rib fracture	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Road traffic accident	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Scratch	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Stress fracture	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Subdural haematoma	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Sunburn	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Thermal burn	1/280 (0.4%)	1	2/70 (2.9%)	2	1/137 (0.7%)	1
Investigations
Alanine aminotransferase increased	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Amylase increased	3/280 (1.1%)	3	0/70 (0%)	0	1/137 (0.7%)	1
Arteriogram coronary	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Aspartate aminotransferase increased	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Blood creatine phosphokinase increased	3/280 (1.1%)	3	0/70 (0%)	0	3/137 (2.2%)	4
Blood triglycerides increased	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Blood uric acid increased	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Blood urine present	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Crystal urine present	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Electrocardiogram t wave abnormal	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Gamma-glutamyltransferase increased	2/280 (0.7%)	2	0/70 (0%)	0	1/137 (0.7%)	1
Lipase increased	10/280 (3.6%)	11	2/70 (2.9%)	2	3/137 (2.2%)	3
Liver function test abnormal	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Monocyte count increased	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Occult blood positive	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Pancreatic enzymes increased	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Prostatic specific antigen increased	0/228 (0%)	0	1/55 (1.8%)	1	0/113 (0%)	0
Skin test positive	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Transaminases increased	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Urine albumin/creatinine ratio increased	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
White blood cell count decreased	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Metabolism and nutrition disorders
Decreased appetite	2/280 (0.7%)	2	2/70 (2.9%)	2	8/137 (5.8%)	8
Dyslipidaemia	1/280 (0.4%)	1	0/70 (0%)	0	2/137 (1.5%)	2
Gout	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Hyperamylasaemia	0/280 (0%)	0	1/70 (1.4%)	2	0/137 (0%)	0
Hyperglycaemia	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Hyperlipidaemia	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Hyperuricaemia	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	4/280 (1.4%)	4	0/70 (0%)	0	1/137 (0.7%)	1
Arthritis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Back pain	8/280 (2.9%)	9	3/70 (4.3%)	3	6/137 (4.4%)	7
Cervical spinal stenosis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Flank pain	1/280 (0.4%)	1	1/70 (1.4%)	1	0/137 (0%)	0
Intervertebral disc protrusion	5/280 (1.8%)	5	0/70 (0%)	0	1/137 (0.7%)	1
Lumbar spinal stenosis	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Muscle fatigue	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Muscle spasms	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Muscular weakness	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Musculoskeletal pain	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Musculoskeletal stiffness	0/280 (0%)	0	1/70 (1.4%)	1	1/137 (0.7%)	1
Myalgia	1/280 (0.4%)	1	1/70 (1.4%)	1	3/137 (2.2%)	3
Myositis	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Osteitis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Osteoarthritis	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Osteoporosis	0/280 (0%)	0	1/70 (1.4%)	1	1/137 (0.7%)	1
Pain in extremity	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Periarthritis	3/280 (1.1%)	3	1/70 (1.4%)	1	1/137 (0.7%)	1
Spinal osteoarthritis	4/280 (1.4%)	4	1/70 (1.4%)	1	0/137 (0%)	0
Tendonitis	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Tenosynovitis	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Trigger finger	1/280 (0.4%)	2	0/70 (0%)	0	0/137 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Duodenal neoplasm	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Meningioma	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Skin papilloma	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Thyroid neoplasm	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Uterine leiomyoma	1/52 (1.9%)	1	1/15 (6.7%)	1	0/24 (0%)	0
Nervous system disorders
Autonomic nervous system imbalance	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Autonomic neuropathy	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Carotid arteriosclerosis	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Cervical radiculopathy	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Cervicobrachial syndrome	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Diabetic neuropathy	1/280 (0.4%)	1	1/70 (1.4%)	1	2/137 (1.5%)	2
Dizziness	1/280 (0.4%)	1	3/70 (4.3%)	3	1/137 (0.7%)	1
Dizziness exertional	1/280 (0.4%)	4	0/70 (0%)	0	0/137 (0%)	0
Head discomfort	1/280 (0.4%)	2	0/70 (0%)	0	0/137 (0%)	0
Headache	2/280 (0.7%)	2	2/70 (2.9%)	2	5/137 (3.6%)	5
Hypoaesthesia	2/280 (0.7%)	2	5/70 (7.1%)	5	1/137 (0.7%)	1
Intercostal neuralgia	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Lacunar infarction	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Paraesthesia	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Radial nerve palsy	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Sciatica	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Somnolence	2/280 (0.7%)	6	0/70 (0%)	0	2/137 (1.5%)	3
Psychiatric disorders
Anxiety disorder	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Insomnia	1/280 (0.4%)	1	2/70 (2.9%)	2	1/137 (0.7%)	1
Irritability	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Sleep disorder	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Renal and urinary disorders
Calculus ureteric	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Calculus urinary	0/280 (0%)	0	1/70 (1.4%)	1	1/137 (0.7%)	1
Cystitis noninfective	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Diabetic nephropathy	4/280 (1.4%)	4	1/70 (1.4%)	1	1/137 (0.7%)	1
Haematuria	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Hypertonic bladder	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Nephrolithiasis	0/280 (0%)	0	0/70 (0%)	0	2/137 (1.5%)	2
Renal cyst	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/228 (0.9%)	2	0/55 (0%)	0	0/113 (0%)	0
Calculus prostatic	0/228 (0%)	0	0/55 (0%)	0	1/113 (0.9%)	1
Cystocele	0/52 (0%)	0	1/15 (6.7%)	1	0/24 (0%)	0
Erectile dysfunction	1/228 (0.4%)	1	0/55 (0%)	0	0/113 (0%)	0
Metrorrhagia	1/52 (1.9%)	1	0/15 (0%)	0	0/24 (0%)	0
Prostatitis	1/228 (0.4%)	1	0/55 (0%)	0	0/113 (0%)	0
Prostatomegaly	0/228 (0%)	0	0/55 (0%)	0	1/113 (0.9%)	1
Rectocele	0/52 (0%)	0	1/15 (6.7%)	1	0/24 (0%)	0
Vulvovaginal pruritus	1/52 (1.9%)	1	0/15 (0%)	0	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Epistaxis	2/280 (0.7%)	2	0/70 (0%)	0	1/137 (0.7%)	1
Hiccups	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Hyperventilation	0/280 (0%)	0	1/70 (1.4%)	2	0/137 (0%)	0
Oropharyngeal discomfort	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Rhinitis allergic	2/280 (0.7%)	2	1/70 (1.4%)	1	4/137 (2.9%)	4
Rhinorrhoea	2/280 (0.7%)	3	0/70 (0%)	0	0/137 (0%)	0
Upper respiratory tract inflammation	4/280 (1.4%)	8	0/70 (0%)	0	3/137 (2.2%)	3
Vasomotor rhinitis	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Skin and subcutaneous tissue disorders
Acne	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Alopecia areata	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	2
Dermal cyst	1/280 (0.4%)	1	1/70 (1.4%)	1	0/137 (0%)	0
Dermatitis	2/280 (0.7%)	2	0/70 (0%)	0	0/137 (0%)	0
Dermatitis contact	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Drug eruption	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Dry skin	1/280 (0.4%)	1	0/70 (0%)	0	1/137 (0.7%)	1
Eczema	4/280 (1.4%)	5	1/70 (1.4%)	1	0/137 (0%)	0
Haemorrhage subcutaneous	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Hyperhidrosis	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Hyperkeratosis	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Miliaria	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Pruritus	4/280 (1.4%)	4	2/70 (2.9%)	3	3/137 (2.2%)	3
Rash	1/280 (0.4%)	1	1/70 (1.4%)	1	2/137 (1.5%)	3
Skin exfoliation	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Skin mass	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Urticaria	0/280 (0%)	0	0/70 (0%)	0	3/137 (2.2%)	5
Social circumstances
Denture wearer	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Surgical and medical procedures
Dental care	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Dental prosthesis placement	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Intra-cerebral aneurysm operation	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Large intestinal polypectomy	3/280 (1.1%)	3	0/70 (0%)	0	0/137 (0%)	0
Limb operation	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Photocoagulation	0/280 (0%)	0	1/70 (1.4%)	1	0/137 (0%)	0
Retinal laser coagulation	1/280 (0.4%)	1	0/70 (0%)	0	0/137 (0%)	0
Tooth extraction	1/280 (0.4%)	1	0/70 (0%)	0	2/137 (1.5%)	3
Tooth repair	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1
Vascular disorders
Hypertension	7/280 (2.5%)	7	2/70 (2.9%)	2	4/137 (2.9%)	4
Orthostatic hypotension	0/280 (0%)	0	0/70 (0%)	0	1/137 (0.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.