EMPOWIR:Enhance the Metabolic Profile of Women With Insulin Resistance
Condition: Hyperinsulinemia; Insulin Resistance; Obesity
MeSH terms: Insulin Resistance; Hyperinsulinism
Intervention: metformin and rosiglitazone
Intervention description: 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
Intervention MeSH terms: Metformin; Rosiglitazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 46.0
Sex: Female
Minimum age: 35 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: hyperinsulinemia; insulin resistance; perimenopause; obesity; overweight; women

Summary:

      The goal of the study is to identify and treat women with midlife weight gain who have normal
      blood sugars, but increased insulin levels (hyperinsulinemia) following the performance of a
      glucose tolerance test. The study will evaluate effects of a unique carbohydrate modified
      diet alone and in combination with metformin(MF) and Avandamet® (MF plus rosiglitazone (RSG))
      on insulin levels in a wide range of ethnically diverse women (aged 35-55) at three academic
      medical centers. The primary study hypothesis is that insulin sensitizing medications, in
      combination with alterations in carbohydrate intake, will reduce insulin levels and improve
      established risk factors for the metabolic syndrome.

      The alarming prevalence of obesity, diabetes, and related comorbidities and the paucity of
      easily adopted, cost-effective preventive strategies for high risk populations, suggest that
      pharmaco-therapies and dietary regimens targeted to reducing insulin resistance could have
      important clinical and public health implications.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy, non-diabetic women with "≥20 pound weight gain since their twenties"

          2. Age: 35-55

          3. Peri-menopausal or postmenopausal status

          4. Body Mass Index (BMI) 25-35 kg/m2

          5. Either:

               1. a single blood pressure recording ≥135/85 or the use of blood pressure medication
                  OR

               2. HDL≤50mg/dl or triglycerides ≥150 mg/dl or the use of lipid modifying medication

          6. Area-under-the-curve (AUC-)insulin level>100mcgU/ml along with normal fasting (≤100
             mg/dl) & postprandial ((≤200 mg/dl) glucose determinations following a 75-gram
             standard oral glucose tolerance test.

             -

        Exclusion Criteria:

          1. known diabetes, fasting blood sugar ≥100 mg/dl or HbA-1-C≥6.0%

          2. known hepatic disease or ALT>40

          3. known renal disease or creatinine ≥ 1.4

          4. known severe pulmonary disease

          5. chronic acidosis of any etiology

          6. Congestive heart failure (NYS Category 1), treated or untreated

          7. Cancer - active within 5 years

          8. current alcoholism or other substance abuse

          9. co-morbid psychiatric disorder, which in the opinion of the screening physician would
             require concomitant psychotherapy as part of obesity management

         10. currently untreated thyroid abnormality (TSH≤0.2 or ≥4mIU/L)

         11. pregnancy or contemplation of pregnancy

         12. use of TZD or metformin within the past year

         13. allergy to TZD or biguanide

         14. use of FDA approved or alternate obesity agent within 6 months of the study

         15. history of pseudotumor cerebri

         16. other impairment, such as a history of medication noncompliance, which in the judgment
             of the screening clinician, would preclude active study participation.

         17. history of known or suspected heart disease