MELT: MEtformin and Lorcaserin for WeighT Loss in Schizophrenia

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02796144
• Collaborator: Columbia University (Other), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 71
• Locations: 4
• Arms: 3
• Duration (Months): 41.4
• Patients Per Site: 17.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Purpose: The purpose of this study is to test new pharmacologic strategies for weight loss in patients with schizophrenia, a population for which no current weight-loss treatments have gained widespread use. The goal is to recruit overweight people with schizophrenia to participate in a 52-week double-blind, randomized study to assess the efficacy and safety of lorcaserin/metformin combination treatment, lorcaserin monotherapy, and placebo on weight, body composition, and measures of glucose and lipid metabolism.

Participants: Approximately 110 subjects will be enrolled at four clinical sites (UNC Chapel Hill, Carolina Behavioral Care, Columbia University, and Augusta University)

Procedures (methods): Behavioral: All participants will be offered a behavioral intervention of weekly diet and exercise counseling aimed at modifying cardiovascular risk factors. This intervention will be provided at all in-person study visits after the Baseline Visit and supplemented with weekly interim phone calls to reinforce lessons between visits. Pharmacological Intervention: All participants who meet entry criteria will be randomized to one of the three treatment groups (lorcaserin/metformin, lorcaserin, and placebo).

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder; Overweight	Drug: Lorcaserin; Drug: Metformin; Drug: Placebo	Phase 4

Detailed Description

Overview of Procedures: All procedures will be conducted at either the UNC Hospitals outpatient clinic in Chapel Hill, NC, at the outpatient North Carolina Psychiatric Research Center (NCPRC), a specialized program of the University of North Carolina Center for Excellence in Community Mental Health in Raleigh, NC, at Carolina Behavioral Care in Hillsborough, NC, at the Lieber Schizophrenia Research Clinic at the New York State Psychiatric Institute (NYSPI) in New York, NY, or at Augusta University in Augusta, GA.

Screening: During the initial clinic visit and after giving informed consent, prospective subjects' psychiatric and medical histories will be reviewed, physical exams conducted, demographics and vital signs taken, and blood and urine collected. Fasting labs will be ordered to measure metabolic parameters (lipid profile, glucose, hemoglobin A1C, insulin and lipids) as well as a complete blood count (CBC), electrolytes, liver/renal function tests, thyroid stimulating hormone (TSH), urinalysis (UA), serum pregnancy test, and urine drug screen (UDS). The Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) will be administered to confirm diagnoses and the Clinical Global Impressions-Severity (CGI-S) will be used to evaluate global psychopathology.

The baseline visit will be scheduled within 28 days of the screening visit. A battery of assessments will be administered including the Clinical Global Impressions-Severity (CGI-S), the Alcohol Use Scale (AUS), Drug Use Scale (DUS), Brief Psychiatric Rating Scale (BPRS), Columbia Suicide Severity Rating Scale (C-SSRS), three assessments to measure eating behavior (Eating Disorder Examination Questionnaire (EDE-Q), Three-Factor Eating Questionnaire (TFEQ), and Food Craving Inventory (FCI)). In addition to the paper pencil assessments, a 24 hour food recall assessment will be administered as a telephone questionnaire by trained personnel from the UNC Nutrition and Obesity Research Center. Accelerometry will also be used to estimate subjects' sedentary and active behavior. Dual-Energy X-ray Absorptiometry (DXA) will also be conducted at the baseline visit (UNC location only). Lastly, the first behavioral intervention lesson will occur at the baseline visit, providing direct lesson instruction and a diary for subjects' to take home for recording their homework and progress.

At the completion of the baseline visit, subjects who continue to meet study inclusion criteria will be randomized to one of the three treatment groups (lorcaserin & metformin, lorcaserin, and placebo). Lorcaserin will be administered in dosages of 10mg with a maximum dose of 20mg. Metformin will be administered in dosages of 500mg with a maximum dose of 2,000mg. In addition, matching placebos will be administered for each drug. Doses will be adjusted based on subject tolerability.

All participants will be offered a behavioral intervention of weekly diet and exercise counseling aimed at modifying cardiovascular risk factors including weight, activity level, blood glucose, blood pressure and lipids. This intervention will be provided by a trained clinician in individualized sessions at all study visits after the Baseline Visit and supplemented with weekly interim phone calls to reinforce lessons between visits. The intervention was adapted from a weight-reduction program developed for patients with severe mental illnesses and was used in the Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (METS) and the Clinical Management of Metabolic Problems in Patients with Schizophrenia: Switching to Aripiprazole versus Continued Treatment with Olanzapine, Quetiapine, or Risperidone (CAMP) trials and is therefore well known to our research group and readily implemented as part of the current proposal.

After study enrollment, subjects will be scheduled for a Week 1 and Week 2 study visit. The purpose of these visits will be to assess medication management (i.e., symptoms, adverse events/side effects, adherence, adjust dose as indicated), collect vital signs, and provide the behavioral therapy intervention. The CGI-S will be completed again at both Week 1 and Week 2, however, the BPRS and C-SSRS will be completed at Week 2 only.

The next 5 study visits will be scheduled as bi-weekly in-person visits. These visits will be similar to Week 1 and Week, 2 with the addition of the Substance Use Scale and Alcohol Use Questionnaire. After the first two behavioral intervention sessions, interim telephone calls will be made between in-person study visits to each participant to reinforce elements of the program and to answer questions.

After the Week 12 study visit, all in-person study visits will transition to monthly visits for the rest of the year. The interim telephone calls will be made bi-weekly between the in-person study visits to each participant to continue to reinforce elements of the program and to answer questions.

At Week 52, all study measures and fasting labs will be collected again.

Vital signs, adverse events, and side effects will be obtained at all in-person study visits. Monitoring labs and appetite regulating hormones will be done at Week 12, Week 24, Week 36, and Week 52.

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Metformin and Lorcaserin for Weight Loss in Schizophrenia
• Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Feb 14, 2020
• Actual Study Completion Date: Feb 14, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lorcaserin and Metformin Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg.	Drug: Lorcaserin; Max dose of 10 mg BID; Other Names: Belviq ; Drug: Metformin; Max dose of 1,000 mg BID; Other Names: Glumetza, Riomet, Glucophage, and Fortamet
Active Comparator: Lorcaserin Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg.	Drug: Lorcaserin; Max dose of 10 mg BID; Other Names: Belviq
Placebo Comparator: Placebo Matching placebos will be administered for each active drug.	Drug: Placebo; Matching placebos will be administered for each drug.; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. Change in Body Weight in Participants Assigned to Lorcaserin/Metformin Combination Treatment and Placebo [Baseline, Last Observed Visit (Up to 52 weeks)]

   Change in body weight in participants assigned to lorcaserin/metformin combination treatment and participants assigned to placebo from baseline to last study visit (up to 52 weeks)

Secondary Outcome Measures

1. Change in Body Weight in Participants Assigned to Lorcaserin Monotherapy Treatment and Placebo [Baseline, Last Observed Visit (Up to 52 weeks)]

   Change in body weight in participants assigned to lorcaserin monotherapy treatment and participants assigned to placebo from baseline to last study visit (up to 52 weeks)

2. Change in HDL Cholesterol [Baseline, Last Observed Visit (Up to 52 weeks)]

   high-density lipoprotein

3. Change in LDL Cholesterol [Baseline, Last Observed Visit (Up to 52 weeks)]

   low-density lipoprotein

4. Change in Triglycerides [Baseline, Last Observed Visit (Up to 52 weeks)]

   serum triglycerides

5. Change in Total Cholesterol [Baseline, Last Observed Visit (Up to 52 weeks)]

   Total Cholesterol

6. Change in Hemoglobin A1c [Baseline, Last Observed Visit (Up to 52 weeks)]

   glycosylated hemoglobin

7. Change in Fasting Glucose [Baseline, Last Observed Visit (Up to 52 weeks)]

   fasting blood glucose

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatients with a diagnosis of schizophrenia or schizoaffective disorder as defined by DSM-IV-TR criteria (see Appendix 3 and Appendix 4) and confirmed by the Structured Clinical Interview for DSM-IV (SCID).

• Duration of psychotic illness must be greater than one year, as defined by having initiated antipsychotic treatment at least 1 year prior to study enrollment.

• Must be 18-65 years of age.

• Must demonstrate adequate decisional capacity to make a choice about participating in this research study and must provide written informed consent to participate.

• BMI greater than or equal to 27 kg/m^2

• Currently treated with one or a combination of two FDA-approved antipsychotic medications (typical or atypical antipsychotics) AND on that drug regimen for at least two months prior to study entry (with stable dosages for at least 1 month).

• Concomitant medications are allowed if agents and doses are unchanged for at least 1 month prior to study entry and if these medications are not among those excluded in the Exclusion Criteria.

• Women who can become pregnant must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized. Acceptable methods include oral, injectable or implanted contraceptives, intrauterine devices or barrier methods such as condoms, diaphragm and spermicides. Women who can become pregnant must have a negative serum pregnancy test at the Screening Visit.

Exclusion Criteria:

• Inpatient status

• Clinical Global Impression Severity (CGI-S) score greater than or equal to 6

• Current treatment with more than 2 antipsychotics

• HbA1c greater than or equal to 6.5%

• Diagnosis of diabetes mellitus or current treatment with insulin or oral hypoglycemics

• Current or prior treatment with metformin within the past 3 months

• Current or prior treatment with lorcaserin within the past 3 months

• Current or prior treatment with a 5-HT2B agonist (e.g. cabergoline) within the past 45 days due to potential risk for heart valve defects

• Current treatment with two or more antidepressants

• Current treatment with a single antidepressant prescribed in excess of the maximum approved dose

• Current treatment with monoamine oxidase inhibitor (MAOI) class of antidepressants (isocarboxazid, phenelzine, selegiline, tranylcypromine)

• Concurrent treatment with any of the following pro-serotonergic drugs: meperidine, buspirone, dextromethorphan, triptans, tramadol, ritonavir, tryptophan, ginseng, St. John's wort

• Diagnosis of congestive heart failure

• Uncorrected thyroid disorder

• Renal impairment as evidenced by estimated glomerular filtration rate (eGFR) 50 mL/min/1.73 m^2

• Hepatic disease (ALT, AST, or GGT > 2 times upper limit of normal (ULN), total bilirubin > 1.2 times ULN)

• Metabolic acidosis (serum CO2 <20 mEq/L)

• Known hypersensitivity to metformin or lorcaserin

• Women who are pregnant or breastfeeding

• Recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material

• Alcohol abuse/dependence as determined by SCID within the past month

• Other serious and unstable medical condition in the judgment of the investigator

• DSM-IV diagnosis of mental retardation or dementia

• Any medication (prescription or non-prescription) used for weight loss must have been discontinued 3 months prior to study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Augusta University	Augusta	Georgia	United States	30912
2	New York State Psychiatric Institute (NYSPI), Columbia University	New York	New York	United States	11032
3	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
4	Carolina Behavioral Care	Hillsborough	North Carolina	United States	27278

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• Columbia University
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Lars F. Jarskog, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 20, 2019

More Information

Publications

• Brar JS, Ganguli R, Pandina G, Turkoz I, Berry S, Mahmoud R. Effects of behavioral therapy on weight loss in overweight and obese patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry. 2005 Feb;66(2):205-12.
• Jarskog LF, Hamer RM, Catellier DJ, Stewart DD, Lavange L, Ray N, Golden LH, Lieberman JA, Stroup TS; METS Investigators. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder. Am J Psychiatry. 2013 Sep;170(9):1032-40. doi: 10.1176/appi.ajp.2013.12010127.
• Stroup TS, McEvoy JP, Ring KD, Hamer RH, LaVange LM, Swartz MS, Rosenheck RA, Perkins DO, Nussbaum AM, Lieberman JA; Schizophrenia Trials Network. A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: comparison of antipsychotics for metabolic problems (CAMP). Am J Psychiatry. 2011 Sep;168(9):947-56. doi: 10.1176/appi.ajp.2011.10111609. Epub 2011 Jul 18.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02796144
• Other Study ID Numbers: 15-1998; 1R01DK105526-01A1
• First Posted: Jun 10, 2016
• Last Update Posted: Mar 3, 2021
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of North Carolina, Chapel Hill: schizophrenia; schizoaffective disorder; overweight; obesity; weight loss; metformin; lorcaserin
• Additional relevant MeSH terms: Overweight; Weight Loss; Schizophrenia; Psychotic Disorders; Metformin

Study Results

Participant Flow

Arm/Group Title	Lorcaserin and Metformin	Lorcaserin	Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
Period Title: Overall Study
STARTED	23	24	24
COMPLETED	18	21	18
NOT COMPLETED	5	3	6

Baseline Characteristics

Arm/Group Title	Lorcaserin and Metformin	Lorcaserin	Placebo	Total
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.	Total of all reporting groups
Overall Participants	23	24	24	71
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	22 95.7%	24 100%	24 100%	70 98.6%
>=65 years	1 4.3%	0 0%	0 0%	1 1.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.52 (11.45)	43.75 (10.16)	38.25 (9.87)	40.85 (10.60)
Sex: Female, Male (Count of Participants)
Female	10 43.5%	5 20.8%	9 37.5%	24 33.8%
Male	13 56.5%	19 79.2%	15 62.5%	47 66.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 4.2%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	12 52.2%	10 41.7%	13 54.2%	35 49.3%
White	9 39.1%	13 54.2%	8 33.3%	30 42.3%
More than one race	1 4.3%	1 4.2%	1 4.2%	3 4.2%
Unknown or Not Reported	1 4.3%	0 0%	1 4.2%	2 2.8%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	3 13%	3 12.5%	4 16.7%	10 14.1%
Not Hispanic or Latino	20 87%	21 87.5%	20 83.3%	61 85.9%
Region of Enrollment (Count of Participants)
United States	23 100%	24 100%	24 100%	71 100%

Outcome Measures

1. Primary Outcome

Title	Change in Body Weight in Participants Assigned to Lorcaserin/Metformin Combination Treatment and Placebo
Description	Change in body weight in participants assigned to lorcaserin/metformin combination treatment and participants assigned to placebo from baseline to last study visit (up to 52 weeks)
Time Frame	Baseline, Last Observed Visit (Up to 52 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lorcaserin and Metformin	Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
Measure Participants	23	24
Mean (Standard Error) [pounds]	-13.05 (2.97)	-3.02 (2.29)

2. Secondary Outcome

Title	Change in Body Weight in Participants Assigned to Lorcaserin Monotherapy Treatment and Placebo
Description	Change in body weight in participants assigned to lorcaserin monotherapy treatment and participants assigned to placebo from baseline to last study visit (up to 52 weeks)
Time Frame	Baseline, Last Observed Visit (Up to 52 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lorcaserin	Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
Measure Participants	24	24
Mean (Standard Error) [pounds]	-5.18 (2.43)	-3.02 (2.29)

3. Secondary Outcome

Title	Change in HDL Cholesterol
Description	high-density lipoprotein
Time Frame	Baseline, Last Observed Visit (Up to 52 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent to treat (MITT) population included all randomized participants. Analyses using the MITT population were based on subjects with both baseline and post-treatment measures.

Arm/Group Title	Lorcaserin and Metformin	Lorcaserin	Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
Measure Participants	20	22	18
Mean (Standard Error) [mg/dL]	3.8 (1.27)	1.45 (1.71)	-0.78 (2.63)

4. Secondary Outcome

Title	Change in LDL Cholesterol
Description	low-density lipoprotein
Time Frame	Baseline, Last Observed Visit (Up to 52 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent to treat (MITT) population included all randomized participants. Analyses using the MITT population were based on subjects with both baseline and post-treatment measures.

Arm/Group Title	Lorcaserin and Metformin	Lorcaserin	Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
Measure Participants	20	22	18
Mean (Standard Error) [mg/dL]	-7.60 (3.87)	-10.86 (5.40)	-6.83 (5.03)

5. Secondary Outcome

Title	Change in Triglycerides
Description	serum triglycerides
Time Frame	Baseline, Last Observed Visit (Up to 52 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent to treat (MITT) population included all randomized participants. Analyses using the MITT population were based on subjects with both baseline and post-treatment measures.

Arm/Group Title	Lorcaserin and Metformin	Lorcaserin	Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
Measure Participants	20	22	19
Mean (Standard Error) [mg/dL]	-18.60 (12.86)	-19.68 (14.97)	-3.11 (13.43)

6. Secondary Outcome

Title	Change in Total Cholesterol
Description	Total Cholesterol
Time Frame	Baseline, Last Observed Visit (Up to 52 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent to treat (MITT) population included all randomized participants. Analyses using the MITT population were based on subjects with both baseline and post-treatment measures.

Arm/Group Title	Lorcaserin and Metformin	Lorcaserin	Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
Measure Participants	20	22	19
Mean (Standard Error) [mg/dL]	-9.05 (3.96)	-13.45 (7.01)	-9.21 (4.83)

7. Secondary Outcome

Title	Change in Hemoglobin A1c
Description	glycosylated hemoglobin
Time Frame	Baseline, Last Observed Visit (Up to 52 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent to treat (MITT) population included all randomized participants. Analyses using the MITT population were based on subjects with both baseline and post-treatment measures.

Arm/Group Title	Lorcaserin and Metformin	Lorcaserin	Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
Measure Participants	20	23	19
Mean (Standard Error) [percentage of glycosylated hemoglobin]	-0.03 (0.05)	0.07 (0.08)	0.05 (0.05)

8. Secondary Outcome

Title	Change in Fasting Glucose
Description	fasting blood glucose
Time Frame	Baseline, Last Observed Visit (Up to 52 weeks)

Outcome Measure Data

Analysis Population Description

The modified intent to treat (MITT) population included all randomized participants. Analyses using the MITT population were based on subjects with both baseline and post-treatment measures.

Arm/Group Title	Lorcaserin and Metformin	Lorcaserin	Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID	Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
Measure Participants	20	22	19
Mean (Standard Error) [mg/dL]	-4.30 (3.75)	-3.27 (2.58)	3.53 (2.11)

Adverse Events

Time Frame	From the time Informed Consent was signed until the last study visit, a total duration of 52 weeks after randomization.
Arm/Group Title	Lorcaserin and Metformin		Lorcaserin		Placebo
Arm/Group Description	Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Metformin will be administered in dosages of 500 mg with a maximum dose of 2,000 mg. Lorcaserin: Max dose of 10 mg BID Metformin: Max dose of 1,000 mg BID		Lorcaserin will be administered in dosages of 10 mg with a maximum dose of 20 mg. Lorcaserin: Max dose of 10 mg BID		Matching placebos will be administered for each active drug. Placebo: Matching placebos will be administered for each drug.
All Cause Mortality
	Lorcaserin and Metformin		Lorcaserin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)		0/24 (0%)
Serious Adverse Events
	Lorcaserin and Metformin		Lorcaserin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)		2/24 (8.3%)		3/24 (12.5%)
Gastrointestinal disorders
Hospitalization due to abdominal pain	0/23 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1
Immune system disorders
Generalized Hives and swelling	1/23 (4.3%)	1	0/24 (0%)	0	0/24 (0%)	0
Psychiatric disorders
Hospitalization due to psychosis exacerbation	0/23 (0%)	0	2/24 (8.3%)	2	1/24 (4.2%)	2
Important Medical Intervention due to transient suicidal ideation	0/23 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Lorcaserin and Metformin		Lorcaserin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/23 (87%)		18/24 (75%)		16/24 (66.7%)
Gastrointestinal disorders
Nausea	5/23 (21.7%)		5/24 (20.8%)		7/24 (29.2%)
Vomiting	5/23 (21.7%)		4/24 (16.7%)		6/24 (25%)
Diarrhea	8/23 (34.8%)		5/24 (20.8%)		5/24 (20.8%)
General disorders
Headache	11/23 (47.8%)		10/24 (41.7%)		8/24 (33.3%)
Dizziness	8/23 (34.8%)		5/24 (20.8%)		5/24 (20.8%)
Fatigue	7/23 (30.4%)		7/24 (29.2%)		13/24 (54.2%)
Restlessness	9/23 (39.1%)		6/24 (25%)		4/24 (16.7%)
Excess sweating	5/23 (21.7%)		2/24 (8.3%)		3/24 (12.5%)
Musculoskeletal and connective tissue disorders
Muscle twitching or spasms	6/23 (26.1%)		5/24 (20.8%)		8/24 (33.3%)
Muscle stiffness	8/23 (34.8%)		8/24 (33.3%)		8/24 (33.3%)
Problems with coordination	5/23 (21.7%)		2/24 (8.3%)		5/24 (20.8%)
Psychiatric disorders
Confusion	4/23 (17.4%)		1/24 (4.2%)		3/24 (12.5%)
Respiratory, thoracic and mediastinal disorders
Upper Respiratory	3/23 (13%)		2/24 (8.3%)		0/24 (0%)
Vascular disorders
Racing heart rate	5/23 (21.7%)		4/24 (16.7%)		5/24 (20.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.