EMPOWIR:Enhance the Metabolic Profile of Women With Insul... | NCT00618072

ID	Type	Description	Link
GSK CRN: 007674

EMPOWIR:Enhance the Metabolic Profile of Women With Insul... | NCT00618072 | Trialant

Sponsor/Collaborators Module

Name	Class
Albert Einstein College of Medicine	OTHER
University of Tennessee	OTHER

Description Module

Detailed Description

Progressive weight gain that starts in the fourth and fifth decades is commonly reported by women from all ethnic and socio-economic groups. Our previous data suggest that, in large and diverse subpopulations of healthy-appearing women this midlife weight gain may represent the earliest clinical manifestation of insulin resistance - demarcated by increased insulin response curves in the presence of completely normal glucose tolerance tests. We termed the disorder Syndrome W to highlight its defining triad of weight gain, waist gain and white-coat hypertension in women and its role as an alphabetic and chronologic antecedent to the better known Syndrome X. As in other disorders of insulin action in younger women, including Polycystic Ovarian Syndrome (PCOS), early adrenarche, and precocious puberty, Syndrome W is, presumably, a harbinger of The Metabolic Syndrome and Type 2 diabetes at an early and optimal period for intervention.

Preliminary data from our first pilot study suggested that metformin, in combination with a hypocaloric, low-fat, carbohydrate modified dietary program produced significant and sustainable weight loss in women with Syndrome W, with notable reductions in fasting insulin levels. These findings supported hypotheses that insulin elevation might be an antecedent, as well as a consequence, of weight gain, accounting for a progressive and intractable weight spiral as women transition from their forties to their sixties. Additional two to four year follow-up in an intention-to-treat analysis of consecutive women who lost ≥10% of their body weight after one year of the treatment regimen further suggests that this composite intervention prevents weight regain and the onset of overt glucose impairment. The protocol evolved from evaluation and treatment of several hundred patients seen in The Endocrine Faculty Practice over a ten year period and has been highly successful in a broad ethnic range of normo-glycemic, hyperinsulinemic subjects. These include midlife women with weight gain and overweight men with upper body obesity - populations which have not been comparably treated in prior studies which focus predominantly on subjects with discernible glycemic abnormalities. The magnitude and duration of the treatment effect suggest that more rigorous study should be undertaken with a randomized clinical trial.

PPAR agonists including thiazolidinediones (TZD's) are a newer category of insulin sensitizers with increasingly wide and well-studied positive attributes, including redistribution of fat depots, increased adiponectin secretion, and reduction of inflammatory and proinflammatory markers.

The combination of metformin and rosiglitazone (Avandamet®) is FDA-approved for the treatment of hyperglycemia in patients with Type 2 diabetes. Previous clinical research and recent laboratory data suggest that the two categories of insulin sensitizers have independent and additive mechanisms of action that could target and, ultimately, modulate the underlying pathogenesis of insulin resistance.

Comparison studies suggest that TZD's may have a greater insulin sensitizing action and provide greater reduction in hyperinsulinemia than metformin. However, due to increased adipocyte expression (and possible other mechanisms), weight gain is a common and undesirable side effect of TZD treatment. The addition of metformin to rosiglitazone, along with dietary strategies that reduce endogenous insulin production could prove an ideal therapeutic option to attenuate insulin resistance and preserve ß-cell function in high risk individuals. Early initiation of this dual regimen in normoglycemic subjects with documented hyperinsulinemia could have profound implications for Syndrome W women and for an additional 25% of the adult US population estimated to have other manifestations of The Metabolic Syndrome.

The primary study question addressed is whether dual treatment regimens which modulate insulin action can reduce hyperinsulinemia and insulin resistance in high risk, but healthy-appearing normoglycemic, hyperinsulinemic subjects identified because of progressive, intractable, midlife weight gain

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
A: Study diet	Placebo Comparator	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.	Drug: metformin and rosiglitazone
B: Study diet plus Metformin	Active Comparator	Metformin and Rosiglitazone Placebo EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.	Drug: metformin and rosiglitazone
C: Study diet plus metformin and avandia	Active Comparator	Metformin and Rosiglitazone EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.	Drug: metformin and rosiglitazone

Interventions

Name	Type	Description	Arm Group Labels	Other Names
metformin and rosiglitazone	Drug	4 week dosage escalation of metformin, 500 mg/day (or placebo) to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day(or placebo) added at weeks 3 and weeks 4 to a a total dose of 4 mg/day

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Fasting Insulin	Insulin was determined with a Siemens Immulite assay with respective intra-and inter-CV's 5.7 and 5.9%, and no cross reactivity to pro-insulin.	6 months

Secondary Outcomes

Measure	Description	Time Frame
Body Weight	Body weight measurement was performed three times and averaged by a single study coordinator.	6 months
HOMA-IR	HOMA-IR was calculated by the formula: fasting insulin (uU/mL) times fasting glucose (mg/L) divided by 22.5.

Contacts/Locations Module

Name	Affiliation	Role
Harriette R Mogul, MD MPH	New York Medical College	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Albert Einstein College of Medicine		The Bronx	New York	10461	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
11975807	Background	Mogul HR, Peterson SJ, Weinstein BI, Zhang S, Southren AL. Metformin and carbohydrate-modified diet: a novel obesity treatment protocol: preliminary findings from a case series of nondiabetic women with midlife weight gain and hyperinsulinemia. Heart Dis. 2001 Sep-Oct;3(5):285-92. doi: 10.1097/00132580-200109000-00002.
11975838

Arm/Group Information

ID	Title	Description
FG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
FG001	B: EMPOWIR Diet Plus Metformin and Placebo Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
FG002	C: EMPOWIR Diet Plus Metformin and Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00016 subjects FG00115 subjects FG00215 subjects
COMPLETED		FG00014 subjects FG00114 subjects FG00211 subjects
NOT COMPLETED		FG0002 subjects FG0011 subjects FG0024 subjects

Type	Comment	Reasons
Lost to Follow-up		FG0002 subjects FG0010 subjects FG0023 subjects
Physician Decision		FG000

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day
BG001

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Fasting Insulin

Insulin was determined with a Siemens Immulite assay with respective intra-and inter-CV's 5.7 and 5.9%, and no cross reactivity to pro-insulin.

The final data-set consisted of 44 study participants, after exclusion of two study completers due to clinical conditions which appeared de novo (asthma requiring high dose prednisone and growth hormone deficiency diagnosed mid-study) - applicable to all study outcomes.

Posted

Mean

Standard Error

uIU/mL

6 months

ID	Title	Description
OG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	A: EMPOWIR and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a a total dose of 4 mg/day

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Worsening of Hypertension	Cardiac disorders		Non-systematic Assessment	One patient with a prior history of hypertension was withdrawn due to elevated BP.

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Harriette R. Mogul MD MPH	New York Medical College	914-594-2278		Harriette_Mogul@NYMC.edu

Condition Browse Module

ID	Term
D006946	Hyperinsulinism
D007333	Insulin Resistance
D009765	Obesity
D050177	Overweight

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D044343	Overnutrition

Intervention Browse Module

ID	Term
C471074	rosiglitazone-metformin combination
D008687	Metformin
D000077154	Rosiglitazone

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals
D045162

Group IDs	Group Description	Statistical Method	P-Value	Tested Non-Inferiority	Non-Inferiority Type
OG000	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test	0.181	No	Superiority or Other
OG001	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test	0.026	No	Superiority or Other
OG002	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test	0.063	No	Superiority or Other

Secondary

Body Weight

Body weight measurement was performed three times and averaged by a single study coordinator.

Posted

Mean

Standard Error

6 months

ID	Title	Description
OG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG001	B: EMPOWIR Diet Plus Metformin and Placebo Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG002	C: EMPOWIR Diet Plus Metformin and Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Units	Counts
Participants	OG00016 OG00114 OG00214

Title

Denominators

Categories

Title	Measurements
	OG00080.0± 2.7 OG00180.4± 2.1 OG00277.5± 4.0

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test		0.049													No	Superiority or Other
OG001	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.

Secondary

HOMA-IR

HOMA-IR was calculated by the formula: fasting insulin (uU/mL) times fasting glucose (mg/L) divided by 22.5.

Posted

Mean

Standard Error

HOMA-IR score

6 months

ID	Title	Description
OG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG001	B: EMPOWIR Diet Plus Metformin and Placebo Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG002	C: EMPOWIR Diet Plus Metformin and Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Units	Counts
Participants	OG00016 OG00114 OG00214

Title

Denominators

Categories

Title	Measurements
	OG0001.5± 0.1 OG0011.6± 0.3 OG0021.3± 0.2

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test		0.142													No	Superiority or Other
OG001	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.

Secondary

Waist Circumference

Posted

Mean

Standard Error

6 months

ID	Title	Description
OG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG001	B: EMPOWIR Diet Plus Metformin and Placebo Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG002	C: EMPOWIR Diet Plus Metformin and Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Units	Counts
Participants	OG00016 OG00114 OG00214

Title

Denominators

Categories

Title	Measurements
	OG00093.1± 2.1 OG00190.4± 1.9 OG00287.5± 3.2

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test		0.052													No	Superiority or Other
OG001	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.

Secondary

Systolic BP

Blood pressure was assessed using NCEP guidelines.

Posted

Mean

Standard Error

mmHg

6 months

ID	Title	Description
OG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG001	B: EMPOWIR Diet Plus Metformin and Placebo Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG002	C: EMPOWIR Diet Plus Metformin and Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Units	Counts
Participants	OG00016 OG00114 OG00214

Title

Denominators

Categories

Title	Measurements
	OG000113.8± 2.9 OG001107.2± 3.0 OG002114.2± 4.7

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test		0.265													No	Superiority or Other
OG001	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.

Secondary

Diastolic BP

Blood pressure was assessed using NCEP guidelines.

Posted

Mean

Standard Error

mmHg

6 months

ID	Title	Description
OG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG001	B: EMPOWIR Diet Plus Metformin and Placebo Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG002	C: EMPOWIR Diet Plus Metformin and Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Units	Counts
Participants	OG00016 OG00114 OG00214

Title

Denominators

Categories

Title	Measurements
	OG00071.7± 2.3 OG00172.7± 2.3 OG00274.3± 3.8

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test		0.025													No	Superiority or Other
OG001	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.

Secondary

HDL

HDL was measured using two reagents homogeneous systems with selective detergents to homogenize the lipoprotein of interest.

Posted

Mean

Standard Error

mg/dl

6 months

ID	Title	Description
OG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG001	B: EMPOWIR Diet Plus Metformin and Placebo Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG002	C: EMPOWIR Diet Plus Metformin and Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Units	Counts
Participants	OG00016 OG00114 OG00214

Title

Denominators

Categories

Title	Measurements
	OG00056.5± 3.5 OG00170.1± 5.8 OG00268.3± 6.2

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test		0.016													No	Superiority or Other
OG001	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.

Secondary

Triglycerides

Triglycerides were measured by enzymatic immunoassay on an AU400 chemistry auto-analyzer with commercially available enzymatic reagents.

Posted

Mean

Standard Error

mg/dl

6 months

ID	Title	Description
OG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG001	B: EMPOWIR Diet Plus Metformin and Placebo Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG002	C: EMPOWIR Diet Plus Metformin and Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Units	Counts
Participants	OG00016 OG00114 OG00214

Title

Denominators

Categories

Title	Measurements
	OG00095.2± 10.7 OG001103.1± 13.0 OG002109.2± 18.3

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test		0.648													No	Superiority or Other
OG001	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.

Secondary

Adiponectin

Total adiponectin was measured with a commercial ELISA kit (Millipore/Linco Research, St. Charles, MO) in the laboratory of Dr. Philipp Scherer.

Posted

Mean

Standard Error

ug/mL

6 months

ID	Title	Description
OG000	A: EMPOWIR Diet and Placebo	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of placebo metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG001	B: EMPOWIR Diet Plus Metformin and Placebo Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of placebo rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.
OG002	C: EMPOWIR Diet Plus Metformin and Avandia	EMPOWIR dietary intervention food exchange program; 40-45% carbohydrates, 35-40% protein, and 20% fat AND 4 week dosage escalation of metformin, 500 mg/day to a total dose of 2000mg/day; starting dose of rosiglitazone 2mg/day added at weeks 3 and weeks 4 to a total dose of 4 mg/day.

Units	Counts
Participants	OG00016 OG00114 OG00214

Title

Denominators

Categories

Title	Measurements
	OG00010.6± 1.2 OG00110.9± 1.7 OG00218.5± 1.5

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.	Paired t-test		0.092													No	Superiority or Other
OG001	Paired t-tests were used to compare within-group mean differences at baseline and at 6 months following randomization for each of the 3 comparator groups.