A Weight Loss Study in Overweight Men and Women

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00993421
• Collaborator: (none)
• Enrollment: 343
• Locations: 21
• Arms: 7
• Duration (Months): 8
• Patients Per Site: 16.3
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if LY377604 + sibutramine work better than LY377604 or sibutramine alone in the treatment of obesity.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: LY377604; Drug: Sibutramine; Drug: Metoprolol; Drug: Placebo sibutramine; Drug: Placebo Metoprolol; Drug: Placebo LY377604	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 343 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: LY377604 + Sibutramine Hydrochloride Monohydrate: A Phase 2 Weight Loss Efficacy Study in Overweight/Obese Men and Women
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo	Drug: Placebo sibutramine; given daily, orally for 24 weeks; Drug: Placebo Metoprolol; given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper); Drug: Placebo LY377604; given daily, orally for 24 weeks
Experimental: LY377604 (75 mg)	Drug: LY377604; Given daily, orally for 24 weeks; Drug: Placebo sibutramine; given daily, orally for 24 weeks; Drug: Placebo Metoprolol; given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
Active Comparator: sibutramine (30 mg)/metoprolol (200 mg)	Drug: Sibutramine; given daily, orally for 24 weeks; Drug: Metoprolol; given daily, orally for 24 weeks (100 mg for 1 week followed by 200 mg for 23 weeks. Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper (1 week at 100 mg/day followed by 1 week at 50 mg/day).
Experimental: LY377604 (40 mg)/sibutramine (30 mg)	Drug: LY377604; Given daily, orally for 24 weeks; Drug: Sibutramine; given daily, orally for 24 weeks; Drug: Placebo Metoprolol; given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
Experimental: LY377604 (75 mg)/sibutramine (30 mg)	Drug: LY377604; Given daily, orally for 24 weeks; Drug: Sibutramine; given daily, orally for 24 weeks; Drug: Placebo Metoprolol; given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
Experimental: LY377604 (15 mg)/sibutramine (30 mg)	Drug: LY377604; Given daily, orally for 24 weeks; Drug: Sibutramine; given daily, orally for 24 weeks; Drug: Placebo Metoprolol; given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)
Experimental: LY377604 (75 mg)/sibutramine (15 mg)	Drug: LY377604; Given daily, orally for 24 weeks; Drug: Sibutramine; given daily, orally for 24 weeks; Drug: Placebo Metoprolol; given daily, orally for 26 weeks (24 weeks plus 2 weeks of taper)

Outcome Measures

Primary Outcome Measures

1. Percent Change in Body Weight From Baseline to 24 Week Endpoint [Baseline, 24 weeks]

   Body weight percentage change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body weight, age, gender were used as covariates.

Secondary Outcome Measures

1. The Mean Change in Body Weight From Baseline to 24 Week Endpoint [Baseline, 24 weeks]

   Body weight change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body weight, age, gender were used as covariates.

2. Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks [24 weeks]

3. Change in Heart Rate From Baseline to 24 Week Endpoint [Baseline, 24 weeks]

   Heart rate change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline heart rate, age, gender were used as covariates.

4. Change in Blood Pressure From Baseline to 24 Week Endpoint [Baseline, 24 weeks]

   Blood pressure change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline blood pressure, age, gender were used as covariates.

5. Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint [Baseline, 24 weeks]

   Change in body composition (lean body mass and fat mass) was assessed using dual energy x-ray absorptiometry (DXA) and is presented as LSMEAN values with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body composition, age, gender were used as covariates.

6. Change in Waist Circumference From Baseline to 24 Week Endpoint [Baseline, 24 weeks]

   Change from baseline to endpoint is presented as LSMEAN with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline waist circumference, age, gender were used as covariates.

7. Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint [Baseline, 24 weeks]

   Percentage change from baseline to endpoint is presented as LSMEAN with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline waist circumference, age, gender were used as covariates.

8. Change in Total Cholesterol From Baseline to 24 Weeks Endpoint [Baseline, 24 weeks]

9. Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint [Baseline, 24 weeks]

10. Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint [Baseline, 24 weeks]

11. Change in Triglycerides From Baseline to 24 Weeks Endpoint [Baseline, 24 weeks]

12. Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL) [Baseline, 24 weeks]

    Results presented as Least Squares Mean with treatment, visit, and their interaction as fixed effects, subject as random effect, baseline body mass index used as covariate. OWL-QoL consists of 17 items on scale ranging from 0 (Not at all) to 6 (A very great deal). Before calculating scores, each item is reversed. A single quality of life score is computed by summing each item and transforming this raw score onto standardized scale of 0 (greatest impact) to 100 (lowest impact) using formula: score = [(sum of component items score (minus) lowest possible score/ possible raw score range)*100].

13. Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale [Baseline, 24 weeks]

    Vitality change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body mass index was used as covariate. SF-36 is a self-reported questionnaire that consists of 36 questions covering 8 health domains including vitality. The vitality domain results are presented. The vitality domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning.

14. Change in Glycated Hemoglobin A1c (HbA1c) From Baseline [Baseline, 24 weeks]

    Analysis of change in HbA1c was not conducted due to an inadequate number of samples.

15. Change in Fasting Glucose From Baseline to 24 Weeks Endpoint [Baseline, 24 weeks]

    Analysis of change in fasting glucose was not conducted due to an inadequate number of samples.

16. Change in Fasting Insulin From Baseline to 24 Weeks Endpoint [Baseline, 24 weeks]

    Analysis of change in fasting insulin was not conducted due to an inadequate number of samples.

17. Change in Insulin Resistance From Baseline to 24 Weeks Endpoint [Baseline, 24 weeks]

    Analysis of change in insulin resistance was not conducted due to an inadequate number of samples.

18. Pharmacokinetics: Area Under the Concentration Time Curve (AUC) [4 weeks, 12 weeks, and 24 weeks]

    Analysis of AUC was not conducted due to an inadequate number of samples collected.

19. Pharmacokinetics: Maximum Concentration (Cmax) [4 weeks, 12 weeks, and 24 weeks]

    Analysis of Cmax was not conducted due to an inadequate number of samples collected.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Are between the body mass index (BMI) of 27 and 45 kg/m^2, inclusive, at the time of screening.

Exclusion Criteria:

• Have a Diastolic Blood Pressure (DBP) greater than 90 mm Hg or less than 55 mm Hg, and/or Systolic Blood Pressure (SBP) >140 mm Hg or <90 mmHg, confirmed by at least 1 repeat measurement. Subjects with hypertension treated with antihypertensive medication are not excluded if blood pressure is within the prescribed limits and they are not treated with excluded medications. Changes in antihypertensive medication are not permitted within 30 days prior to randomization

• Previous history of poorly controlled hypertension, (that is, >160/100 or hypertension which requires more than 2 drugs for control).

• Have a pulse rate >90 bpm or <50 bpm.

• Evidence or history of prior significant cardiovascular disease, coronary artery disease, cardiovascular surgery, significant valvular disease, heart failure, arrhythmias, sick sinus syndrome or stroke.

• Current treatment with β-blockers, calcium channel blockers, digitalis glycosides (for example, digoxin, etc), or clonidine.

• Recent treatment (within 2 weeks prior to randomization) with catecholamine-depleting drugs (such as reserpine or tetrabenazine, monoamine oxidase inhibitors (MAOIs).

• Current treatment with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRI), any drug that is a serotonin, norepinephrine, or dopamine reuptake inhibitor, "triptan" or ergot therapies for migraine or nausea, or serotonin-releasing agents.

• Treatment with significant inhibitors of Cytochrome P2D6 (CYP2D6), such as bupropion, fluoxetine, paroxetine, quinidine, duloxetine, amiodarone, cimetidine, chlorpheniramine, clomipramine, doxepin, haloperidol, methadone, mibefradil, and ritonavir.

• Participants with bronchospastic diseases or who are treated with bronchodilators or other prescription or nonprescription beta adrenergic agonists.

• Peripheral vascular disease

• History of thyrotoxicosis

• History of seizures (except for childhood febrile convulsion) or at increased risk of seizures (for example, history of significant head trauma or intracranial surgery).

• Have had a significant change in weight, defined as a gain or loss of at least 4 kg (9 lb) in the 90 days prior to randomization

• Have had bariatric surgery (for example, gastric banding or gastric bypass)

• Have had liposuction within 90 days prior to randomization

• Have a disease that affects adipose mass or distribution of energy balance (for example, Cushing's syndrome, uncontrolled hyper- or hypothyroidism).

• Have taken in the 30 days prior to randomization, a medication, herbal product, or nutritional supplement that affects adipose mass or distribution or energy balance, such as glucocorticoids, antiretrovirals, atypical antipsychotics, lithium, valproic acid, lamotrigine, or other anticonvulsants, mirtazapine, bupropion, phentermine, sibutramine, orlistat, rimonabant, amphetamine, or ephedra-containing supplements. Note: Medications that have small and transient effects on weight or medications that may affect weight independent of adipose mass (for example, estrogens or diuretics), may be continued, but may not be started, stopped, or changed during the course of the study.

• Have been diagnosed with an eating disorder, such as anorexia, bulimia, binge eating disorder, or nocturnal eating disorder.

• Have diabetes mellitus treated with medication, or type 2 diabetes mellitus managed with diet and exercise with hemoglobin A1c (HbA1C) >7.0%.

• Symptomatic cholelithiasis in the 90 days prior to randomization.

• Any lifetime history of suicide attempt.

• History of major depressive disorder in the last 2 years or any lifetime history of severe psychiatric disorders (for example, schizophrenia or bipolar disorder).

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.	Mesa	Arizona	United States	85201
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.	Concord	California	United States	94520
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.	La Jolla	California	United States	92037
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.	Waterbury	Connecticut	United States	06708
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.	South Miami	Florida	United States	33143
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.	Idaho Falls	Idaho	United States	83404
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.	Avon	Indiana	United States	46123
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.	Bloomington	Indiana	United States	47403
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.	Carmel	Indiana	United States	46032
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.	Indianapolis	Indiana	United States	46260
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.	Des Moines	Iowa	United States	50314
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.	Topeka	Kansas	United States	66606
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.	Baton Rouge	Louisiana	United States	70808
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.	Haverhill	Massachusetts	United States	01830
15	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.	Sterling Heights	Michigan	United States	48314
16	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.	Minneapolis	Minnesota	United States	55416
17	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.	Las Vegas	Nevada	United States	89130
18	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.	Wilmington	North Carolina	United States	28401
19	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.	Portland	Oregon	United States	97210
20	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.	Dallas	Texas	United States	75230
21	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.	Richmond	Virginia	United States	23233

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.

• ClinicalTrials.gov Identifier: NCT00993421
• Other Study ID Numbers: 11892; I1L-MC-GAEB
• First Posted: Oct 12, 2009
• Last Update Posted: Jun 3, 2011
• Last Verified: Jun 1, 2011

• Additional relevant MeSH terms: Overweight; Weight Loss; Sibutramine; Metoprolol

Study Results

Participant Flow

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Period Title: Overall Study
STARTED	49	49	48	49	52	50	46
COMPLETED	5	4	5	4	6	4	4
NOT COMPLETED	44	45	43	45	46	46	42

Baseline Characteristics

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)	Total
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	Total of all reporting groups
Overall Participants	49	49	48	49	52	50	46	343
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.71 (10.86)	43.89 (11.02)	44.68 (12.00)	43.42 (11.06)	44.15 (10.71)	45.80 (9.15)	43.93 (10.15)	44.09 (10.68)
Sex: Female, Male (Count of Participants)
Female	41 83.7%	42 85.7%	38 79.2%	39 79.6%	40 76.9%	41 82%	34 73.9%	275 80.2%
Male	8 16.3%	7 14.3%	10 20.8%	10 20.4%	12 23.1%	9 18%	12 26.1%	68 19.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 2%	0 0%	1 2%	0 0%	2 0.6%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	1 2%	0 0%	0 0%	1 2.2%	2 0.6%
Black or African American	12 24.5%	5 10.2%	8 16.7%	10 20.4%	8 15.4%	6 12%	7 15.2%	56 16.3%
White	36 73.5%	43 87.8%	39 81.3%	34 69.4%	43 82.7%	42 84%	36 78.3%	273 79.6%
More than one race	1 2%	1 2%	1 2.1%	3 6.1%	1 1.9%	1 2%	2 4.3%	10 2.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	49 100%	49 100%	48 100%	49 100%	52 100%	50 100%	46 100%	343 100%
Height (centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters (cm)]	166.10 (8.02)	166.86 (8.40)	167.51 (9.22)	165.23 (8.93)	168.13 (7.88)	168.99 (8.18)	168.38 (7.50)	167.32 (8.34)
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	97.92 (18.73)	97.15 (15.67)	102.25 (17.80)	96.36 (18.08)	99.09 (17.73)	100.96 (17.20)	100.09 (17.11)	99.10 (17.46)
Body Mass Index (BMI) (kilograms/square meters (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms/square meters (kg/m^2)]	35.22 (4.96)	34.78 (4.53)	36.34 (5.36)	35.12 (4.55)	34.86 (4.39)	35.30 (4.44)	35.22 (4.87)	35.26 (4.71)
Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Systolic Blood Pressure (SBP)	117.11 (11.53)	115.72 (10.78)	117.35 (10.13)	118.67 (11.11)	118.34 (11.37)	119.86 (11.42)	120.72 (11.36)	118.24 (11.13)
Diastolic Blood Pressure (DBP)	75.12 (7.31)	74.40 (7.70)	75.83 (6.76)	76.61 (7.07)	76.94 (6.31)	77.87 (6.82)	78.38 (6.23)	76.44 (6.97)
Waist and Hip Circumference (centimeters (cm)) [Mean (Standard Deviation) ]
Waist Circumference	109.13 (14.10)	107.42 (10.70)	111.47 (12.58)	107.31 (12.06)	110.18 (10.80)	109.99 (11.49)	109.15 (12.95)	109.24 (12.10)
Hip Circumference	119.76 (12.36)	118.55 (9.42)	120.29 (11.51)	117.65 (11.13)	117.30 (14.96)	119.43 (11.45)	118.01 (11.43)	118.70 (11.83)

Outcome Measures

1. Primary Outcome

Title	Percent Change in Body Weight From Baseline to 24 Week Endpoint
Description	Body weight percentage change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body weight, age, gender were used as covariates.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	28	26	24	25	32	22	23
Least Squares Mean (Standard Error) [percent change]	-2.21 (0.81)	0.48 (0.84)	-6.12 (0.86)	-8.53 (0.80)	-6.61 (0.79)	-7.05 (0.85)	-4.71 (0.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY377604 (75 mg), LY377604 (15 mg)/Sibutramine (30 mg)
	Comments	Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY377604 (75 mg), LY377604 (40 mg)/Sibutramine (30 mg)
	Comments	Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LY377604 (75 mg), LY377604 (75 mg)/Sibutramine (30 mg)
	Comments	Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LY377604 (75 mg), LY377604 (75 mg)/Sibutramine (15 mg)
	Comments	Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Sibutramine (30 mg)/Metoprolol (200 mg), LY377604 (15 mg)/Sibutramine (30 mg)
	Comments	Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Sibutramine (30 mg)/Metoprolol (200 mg), LY377604 (40 mg)/Sibutramine (30 mg)
	Comments	Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.668
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Sibutramine (30 mg)/Metoprolol (200 mg), LY377604 (75 mg)/Sibutramine (30 mg)
	Comments	Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.437
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Sibutramine (30 mg)/Metoprolol (200 mg), LY377604 (75 mg)/Sibutramine (15 mg)
	Comments	Hypothesis: Treatment with a combination of LY377604 + sibutramine for 24 weeks would result in weight loss that was significantly greater than treatment with either sibutramine or LY377604 alone.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.249
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	The Mean Change in Body Weight From Baseline to 24 Week Endpoint
Description	Body weight change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body weight, age, gender were used as covariates.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	28	26	24	25	32	22	23
Least Squares Mean (Standard Error) [kilograms]	-2.37 (0.82)	0.45 (0.85)	-6.41 (0.87)	-8.15 (0.81)	-6.49 (0.79)	-7.06 (0.85)	-4.68 (0.87)

3. Secondary Outcome

Title	Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	49	49	48	49	52	50	46
Number [percentage of participants]	10.2 20.8%	0.0 0%	18.8 39.2%	34.7 70.8%	21.2 40.8%	18.0 36%	6.5 14.1%

4. Secondary Outcome

Title	Change in Heart Rate From Baseline to 24 Week Endpoint
Description	Heart rate change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline heart rate, age, gender were used as covariates.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	30	27	24	26	33	22	25
Least Squares Mean (Standard Error) [beats per minute (bpm)]	-0.69 (1.51)	-3.34 (1.60)	-1.37 (1.67)	6.11 (1.60)	2.19 (1.44)	-2.66 (1.72)	-2.46 (1.63)

5. Secondary Outcome

Title	Change in Blood Pressure From Baseline to 24 Week Endpoint
Description	Blood pressure change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline blood pressure, age, gender were used as covariates.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	30	27	24	26	33	22	25
Systolic Blood Pressure	-2.84 (1.67)	-3.59 (1.75)	-3.77 (1.84)	3.25 (1.76)	-1.17 (1.59)	-0.43 (1.90)	0.95 (1.80)
Diastolic Blood Pressure	-2.25 (1.28)	-3.84 (1.35)	-2.51 (1.41)	2.03 (1.34)	0.13 (1.22)	-2.87 (1.45)	-0.38 (1.38)

6. Secondary Outcome

Title	Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint
Description	Change in body composition (lean body mass and fat mass) was assessed using dual energy x-ray absorptiometry (DXA) and is presented as LSMEAN values with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body composition, age, gender were used as covariates.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	28	23	23	23	31	21	25
Fat Mass	-2.40 (0.72)	0.54 (0.76)	-3.00 (0.75)	-6.13 (0.71)	-4.80 (0.67)	-4.29 (0.77)	-2.55 (0.73)
Lean Mass	-0.55 (0.41)	0.15 (0.45)	-1.92 (0.45)	-1.85 (0.43)	-0.71 (0.39)	-1.08 (0.47)	-1.48 (0.43)

7. Secondary Outcome

Title	Change in Waist Circumference From Baseline to 24 Week Endpoint
Description	Change from baseline to endpoint is presented as LSMEAN with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline waist circumference, age, gender were used as covariates.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants receiving at least 1 dose of the study drug according to the treatment the participants actually received. Participants with baseline and a measurement at endpoint were included in the analysis.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	31	27	24	25	32	22	25
Least Squares Mean (Standard Error) [centimeter (cm)]	-6.58 (2.44)	-2.51 (2.62)	-8.84 (2.77)	-6.76 (2.71)	-3.57 (2.38)	-3.55 (2.88)	-8.67 (2.68)

8. Secondary Outcome

Title	Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint
Description	Percentage change from baseline to endpoint is presented as LSMEAN with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline waist circumference, age, gender were used as covariates.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	31	27	24	25	32	22	25
Least Squares Mean (Standard Deviation) [percent change]	-5.86 (2.21)	-2.22 (2.38)	-7.55 (2.52)	-5.96 (2.46)	-3.02 (2.16)	-3.11 (2.62)	-7.29 (2.44)

9. Secondary Outcome

Title	Change in Total Cholesterol From Baseline to 24 Weeks Endpoint
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	48	49	45	49	48	50	43
Mean (Standard Deviation) [millimole/Liter (mmol/L)]	-0.12 (0.68)	-0.13 (0.47)	-0.04 (0.69)	-0.01 (0.67)	0.00 (0.68)	0.17 (0.70)	-0.13 (0.76)

10. Secondary Outcome

Title	Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	48	49	45	49	48	50	43
Mean (Standard Deviation) [millimole/Liter (mmol/L)]	-0.02 (0.16)	-0.05 (0.19)	-0.03 (0.15)	0.01 (0.15)	0.06 (0.21)	0.01 (0.17)	-0.04 (0.17)

11. Secondary Outcome

Title	Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	48	49	45	49	48	49	43
Mean (Standard Deviation) [millimole/Liter (mmol/L)]	-0.07 (0.57)	-0.03 (0.44)	0.00 (0.62)	-0.00 (0.58)	-0.07 (0.50)	0.16 (0.65)	-0.16 (0.67)

12. Secondary Outcome

Title	Change in Triglycerides From Baseline to 24 Weeks Endpoint
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	48	49	45	49	48	50	43
Mean (Standard Deviation) [millimole/Liter (mmol/L)]	-0.06 (0.61)	-0.11 (0.48)	-0.04 (0.66)	0.04 (0.60)	0.04 (0.55)	0.03 (0.72)	0.22 (0.94)

13. Secondary Outcome

Title	Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL)
Description	Results presented as Least Squares Mean with treatment, visit, and their interaction as fixed effects, subject as random effect, baseline body mass index used as covariate. OWL-QoL consists of 17 items on scale ranging from 0 (Not at all) to 6 (A very great deal). Before calculating scores, each item is reversed. A single quality of life score is computed by summing each item and transforming this raw score onto standardized scale of 0 (greatest impact) to 100 (lowest impact) using formula: score = [(sum of component items score (minus) lowest possible score/ possible raw score range)*100].
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	31	26	24	26	34	23	26
Least Squares Mean (Standard Error) [units on a scale]	11.71 (4.93)	2.67 (5.30)	13.96 (5.26)	16.52 (5.27)	17.44 (5.17)	13.53 (5.35)	14.02 (5.23)

14. Secondary Outcome

Title	Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale
Description	Vitality change from baseline is presented as Least Squares Mean (LSMean) with treatment, visit, and their interaction as fixed effects, subject as a random effect, baseline body mass index was used as covariate. SF-36 is a self-reported questionnaire that consists of 36 questions covering 8 health domains including vitality. The vitality domain results are presented. The vitality domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat (IIT) population: all randomized participants who received at least one dose of study drug and received the intended study drug. Participants with baseline and at least one post-baseline measurement were included in the analysis (LOCF).

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	31	27	24	25	34	24	26
Least Squares Mean (Standard Error) [units on a scale]	10.79 (5.24)	5.83 (5.66)	16.81 (5.63)	10.69 (5.69)	7.35 (5.53)	10.62 (5.72)	13.61 (5.58)

15. Secondary Outcome

Title	Change in Glycated Hemoglobin A1c (HbA1c) From Baseline
Description	Analysis of change in HbA1c was not conducted due to an inadequate number of samples.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed due to the small sample size.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	0	0	0	0	0	0	0

16. Secondary Outcome

Title	Change in Fasting Glucose From Baseline to 24 Weeks Endpoint
Description	Analysis of change in fasting glucose was not conducted due to an inadequate number of samples.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed due to an inadequate number of samples.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	0	0	0	0	0	0	0

17. Secondary Outcome

Title	Change in Fasting Insulin From Baseline to 24 Weeks Endpoint
Description	Analysis of change in fasting insulin was not conducted due to an inadequate number of samples.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed due to an inadequate number of samples.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	0	0	0	0	0	0	0

18. Secondary Outcome

Title	Change in Insulin Resistance From Baseline to 24 Weeks Endpoint
Description	Analysis of change in insulin resistance was not conducted due to an inadequate number of samples.
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed due to inadequate number of samples.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	0	0	0	0	0	0	0

19. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration Time Curve (AUC)
Description	Analysis of AUC was not conducted due to an inadequate number of samples collected.
Time Frame	4 weeks, 12 weeks, and 24 weeks

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed because of the low sample size.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	0	0	0	0	0	0	0

20. Secondary Outcome

Title	Pharmacokinetics: Maximum Concentration (Cmax)
Description	Analysis of Cmax was not conducted due to an inadequate number of samples collected.
Time Frame	4 weeks, 12 weeks, and 24 weeks

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed due to the small sample size.

Arm/Group Title	Placebo	LY377604 (75 mg)	Sibutramine (30 mg)/Metoprolol (200 mg)	LY377604 (15 mg)/Sibutramine (30 mg)	LY377604 (40 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (30 mg)	LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.	Given orally, daily for 24 weeks.	sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by a 2 week taper - 1 week at 100 mg/day followed by 1 week at 50 mg/day. Placebo LY377604: given orally, daily for 24 weeks.	LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks.	LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.	LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
Measure Participants	0	0	0	0	0	0	0

Adverse Events

Arm/Group Title	Placebo		LY377604 (75 mg)		Sibutramine (30mg)/Metoprolol (200mg)		LY377604 (15 mg)/Sibutramine (30 mg)		LY377604 (40 mg)/Sibutramine (30 mg)		LY377604 (75 mg)/Sibutramine (30 mg)		LY377604 (75 mg)/Sibutramine (15 mg)
Arm/Group Description	Placebo LY377604: given orally, daily for 24 weeks. Placebo sibutramine: given orally, daily for 24 weeks. Placebo metoprolol: given orally, daily for 24 weeks, followed by 2 week taper.		Given orally, daily for 24 weeks.		sibutramine (30 mg): Given orally, daily for 24 weeks. metoprolol (200 mg): Given orally, daily 100 mg for 1 week followed by 200 mg for 23 weeks (Patients unable to tolerate 200 mg will be dose reduced to 100 mg), followed by 2 week taper (1 week at 100 mg/day followed by 1 week at 50 mg/day). Placebo LY377604: given orally, daily for 24 weeks.		LY377604 (15 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.		LY377604 (40 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.		LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (30 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.		LY377604 (75 mg): Given orally, daily for 24 weeks. sibutramine (15 mg): Given orally, daily for 24 weeks. Placebo metoprolol: Given orally, daily for 24 weeks, followed by 2 week taper.
All Cause Mortality
	Placebo		LY377604 (75 mg)		Sibutramine (30mg)/Metoprolol (200mg)		LY377604 (15 mg)/Sibutramine (30 mg)		LY377604 (40 mg)/Sibutramine (30 mg)		LY377604 (75 mg)/Sibutramine (30 mg)		LY377604 (75 mg)/Sibutramine (15 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		LY377604 (75 mg)		Sibutramine (30mg)/Metoprolol (200mg)		LY377604 (15 mg)/Sibutramine (30 mg)		LY377604 (40 mg)/Sibutramine (30 mg)		LY377604 (75 mg)/Sibutramine (30 mg)		LY377604 (75 mg)/Sibutramine (15 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/49 (0%)		2/48 (4.2%)		2/49 (4.1%)		0/52 (0%)		1/50 (2%)		2/46 (4.3%)
Gastrointestinal disorders
Haemorrhoids	0/49 (0%)	0	0/49 (0%)	0	1/48 (2.1%)	1	0/49 (0%)	0	0/52 (0%)	0	0/50 (0%)	0	0/46 (0%)	0
Vomiting	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	1/49 (2%)	1	0/52 (0%)	0	0/50 (0%)	0	0/46 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	1/49 (2%)	1	0/52 (0%)	0	0/50 (0%)	0	0/46 (0%)	0
Infections and infestations
Meningitis viral	0/49 (0%)	0	0/49 (0%)	0	1/48 (2.1%)	1	0/49 (0%)	0	0/52 (0%)	0	0/50 (0%)	0	0/46 (0%)	0
Injury, poisoning and procedural complications
Head injury	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	0/49 (0%)	0	0/52 (0%)	0	0/50 (0%)	0	1/46 (2.2%)	1
Investigations
Blood pressure decreased	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	0/49 (0%)	0	0/52 (0%)	0	0/50 (0%)	0	1/46 (2.2%)	1
Nervous system disorders
Paraesthesia	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	1/49 (2%)	1	0/52 (0%)	0	0/50 (0%)	0	0/46 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	0/49 (0%)	0	0/52 (0%)	0	1/50 (2%)	1	0/46 (0%)	0
Skin and subcutaneous tissue disorders
Hypoaesthesia facial	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	1/49 (2%)	1	0/52 (0%)	0	0/50 (0%)	0	0/46 (0%)	0
Vascular disorders
Deep vein thrombosis	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	0/49 (0%)	0	0/52 (0%)	0	1/50 (2%)	1	0/46 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		LY377604 (75 mg)		Sibutramine (30mg)/Metoprolol (200mg)		LY377604 (15 mg)/Sibutramine (30 mg)		LY377604 (40 mg)/Sibutramine (30 mg)		LY377604 (75 mg)/Sibutramine (30 mg)		LY377604 (75 mg)/Sibutramine (15 mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/49 (83.7%)		39/49 (79.6%)		38/48 (79.2%)		44/49 (89.8%)		43/52 (82.7%)		46/50 (92%)		33/46 (71.7%)
Eye disorders
Vision blurred	0/49 (0%)	0	1/49 (2%)	1	1/48 (2.1%)	1	0/49 (0%)	0	1/52 (1.9%)	1	0/50 (0%)	0	3/46 (6.5%)	3
Gastrointestinal disorders
Abdominal discomfort	2/49 (4.1%)	2	2/49 (4.1%)	2	0/48 (0%)	0	2/49 (4.1%)	2	3/52 (5.8%)	4	0/50 (0%)	0	1/46 (2.2%)	1
Constipation	4/49 (8.2%)	4	2/49 (4.1%)	2	11/48 (22.9%)	11	9/49 (18.4%)	9	7/52 (13.5%)	8	5/50 (10%)	5	2/46 (4.3%)	2
Diarrhoea	2/49 (4.1%)	2	3/49 (6.1%)	3	1/48 (2.1%)	1	3/49 (6.1%)	3	3/52 (5.8%)	3	5/50 (10%)	6	2/46 (4.3%)	2
Dry mouth	1/49 (2%)	1	4/49 (8.2%)	4	6/48 (12.5%)	6	20/49 (40.8%)	20	16/52 (30.8%)	16	10/50 (20%)	12	8/46 (17.4%)	9
Nausea	3/49 (6.1%)	5	0/49 (0%)	0	3/48 (6.3%)	3	4/49 (8.2%)	5	2/52 (3.8%)	2	3/50 (6%)	3	2/46 (4.3%)	4
Vomiting	5/49 (10.2%)	5	0/49 (0%)	0	1/48 (2.1%)	1	2/49 (4.1%)	2	1/52 (1.9%)	1	1/50 (2%)	1	0/46 (0%)	0
General disorders
Asthenia	1/49 (2%)	1	0/49 (0%)	0	1/48 (2.1%)	1	3/49 (6.1%)	3	2/52 (3.8%)	2	2/50 (4%)	2	0/46 (0%)	0
Fatigue	2/49 (4.1%)	2	5/49 (10.2%)	5	2/48 (4.2%)	2	1/49 (2%)	1	5/52 (9.6%)	5	1/50 (2%)	1	4/46 (8.7%)	4
Infections and infestations
Nasopharyngitis	5/49 (10.2%)	5	5/49 (10.2%)	5	2/48 (4.2%)	2	2/49 (4.1%)	2	1/52 (1.9%)	1	4/50 (8%)	4	2/46 (4.3%)	2
Sinusitis	2/49 (4.1%)	3	2/49 (4.1%)	2	2/48 (4.2%)	2	2/49 (4.1%)	2	3/52 (5.8%)	3	0/50 (0%)	0	0/46 (0%)	0
Upper respiratory tract infection	5/49 (10.2%)	5	6/49 (12.2%)	9	4/48 (8.3%)	4	2/49 (4.1%)	2	4/52 (7.7%)	4	4/50 (8%)	4	5/46 (10.9%)	7
Urinary tract infection	3/49 (6.1%)	3	2/49 (4.1%)	2	3/48 (6.3%)	3	3/49 (6.1%)	3	0/52 (0%)	0	4/50 (8%)	4	4/46 (8.7%)	4
Viral infection	1/49 (2%)	1	1/49 (2%)	2	1/48 (2.1%)	1	5/49 (10.2%)	6	2/52 (3.8%)	3	0/50 (0%)	0	2/46 (4.3%)	2
Injury, poisoning and procedural complications
Muscle strain	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	3/49 (6.1%)	3	3/52 (5.8%)	3	0/50 (0%)	0	2/46 (4.3%)	2
Investigations
Blood creatine phosphokinase increased	2/49 (4.1%)	2	1/49 (2%)	1	0/48 (0%)	0	3/49 (6.1%)	3	0/52 (0%)	0	0/50 (0%)	0	0/46 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/49 (2%)	1	1/49 (2%)	1	1/48 (2.1%)	1	2/49 (4.1%)	2	4/52 (7.7%)	4	2/50 (4%)	2	1/46 (2.2%)	1
Increased appetite	1/49 (2%)	1	3/49 (6.1%)	3	0/48 (0%)	0	0/49 (0%)	0	0/52 (0%)	0	1/50 (2%)	1	0/46 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/49 (2%)	1	4/49 (8.2%)	4	3/48 (6.3%)	3	3/49 (6.1%)	3	1/52 (1.9%)	1	3/50 (6%)	4	0/46 (0%)	0
Back pain	1/49 (2%)	1	0/49 (0%)	0	3/48 (6.3%)	3	4/49 (8.2%)	4	2/52 (3.8%)	2	1/50 (2%)	1	0/46 (0%)	0
Pain in extremity	4/49 (8.2%)	4	1/49 (2%)	1	1/48 (2.1%)	1	0/49 (0%)	0	1/52 (1.9%)	1	1/50 (2%)	1	2/46 (4.3%)	2
Nervous system disorders
Dizziness	2/49 (4.1%)	2	3/49 (6.1%)	3	4/48 (8.3%)	4	4/49 (8.2%)	4	7/52 (13.5%)	8	6/50 (12%)	6	1/46 (2.2%)	1
Dysgeusia	0/49 (0%)	0	1/49 (2%)	1	1/48 (2.1%)	1	1/49 (2%)	1	1/52 (1.9%)	1	3/50 (6%)	3	0/46 (0%)	0
Headache	4/49 (8.2%)	4	3/49 (6.1%)	3	5/48 (10.4%)	5	5/49 (10.2%)	5	5/52 (9.6%)	6	4/50 (8%)	4	2/46 (4.3%)	2
Hypoaesthesia	2/49 (4.1%)	3	3/49 (6.1%)	5	0/48 (0%)	0	1/49 (2%)	1	2/52 (3.8%)	2	0/50 (0%)	0	1/46 (2.2%)	1
Migraine	0/49 (0%)	0	3/49 (6.1%)	3	1/48 (2.1%)	1	1/49 (2%)	1	0/52 (0%)	0	0/50 (0%)	0	0/46 (0%)	0
Sinus headache	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	1/49 (2%)	1	0/52 (0%)	0	3/50 (6%)	3	0/46 (0%)	0
Psychiatric disorders
Anxiety	2/49 (4.1%)	3	0/49 (0%)	0	2/48 (4.2%)	2	1/49 (2%)	1	4/52 (7.7%)	4	0/50 (0%)	0	0/46 (0%)	0
Insomnia	2/49 (4.1%)	2	5/49 (10.2%)	5	3/48 (6.3%)	3	8/49 (16.3%)	8	7/52 (13.5%)	7	6/50 (12%)	6	2/46 (4.3%)	2
Stress	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	0/49 (0%)	0	3/52 (5.8%)	3	0/50 (0%)	0	0/46 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/49 (4.1%)	2	2/49 (4.1%)	2	1/48 (2.1%)	1	4/49 (8.2%)	4	1/52 (1.9%)	1	1/50 (2%)	1	1/46 (2.2%)	1
Dyspnoea	0/49 (0%)	0	1/49 (2%)	1	0/48 (0%)	0	3/49 (6.1%)	3	0/52 (0%)	0	0/50 (0%)	0	1/46 (2.2%)	1
Oropharyngeal pain	0/49 (0%)	0	0/49 (0%)	0	1/48 (2.1%)	1	5/49 (10.2%)	5	3/52 (5.8%)	4	2/50 (4%)	2	1/46 (2.2%)	2
Sinus congestion	1/49 (2%)	1	1/49 (2%)	1	0/48 (0%)	0	3/49 (6.1%)	3	1/52 (1.9%)	1	2/50 (4%)	2	1/46 (2.2%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/49 (0%)	0	0/49 (0%)	0	0/48 (0%)	0	1/49 (2%)	1	2/52 (3.8%)	2	3/50 (6%)	3	0/46 (0%)	0
Rash	0/49 (0%)	0	0/49 (0%)	0	1/48 (2.1%)	1	2/49 (4.1%)	2	4/52 (7.7%)	4	1/50 (2%)	1	1/46 (2.2%)	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.