Exenatide and Metformin Therapy in Overweight Women With PCOS
Condition: Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Overweight; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      Current research has shown that the use of diabetes management practices aimed at reducing
      insulin resistance and hyperinsulinemia (such as weight reduction and the administration of
      oral antidiabetic drugs) in women with PCOS can not only improve glucose and lipid metabolism
      but can also reverse testosterone abnormalities and restore menstrual cycles. A new medicine
      called exenatide (Byetta) has been found to reduce body weight, as well as, improve abnormal
      glucose metabolism in diabetics. This randomized study will compare Exenatide (Byetta) to
      extended release metformin (Fortamet) to combination therapy (both Byetta and Fortamet) on
      menstrual cyclicity, hormone profiles and metabolic profiles over a 24-week period in women
      with PCOS.
    

Detailed description: 
      Objectives: The objective of the present proposal is to compare the clinical, endocrine and
      metabolic effects of therapy with exenatide and metformin alone, to combination therapy in
      women with PCOS. This study will serve as a pilot investigation to open perspectives for
      future investigations combining insulin-sensitizing drugs with different mechanisms of action
      in patients with PCOS, especially ones for whom standard treatment with metformin is less
      effective.

      Subjects : 60 oligomenorrheic overweight/obese (BMI >27) women meeting criteria for PCOS (age
      18-40)· six or fewer menses /year or amenorrheic· clinical or laboratory evidence of
      hyperandrogenism (hirsutism or elevated testosterone (T))· PCOS ovary on ultrasound(need to
      meet criteria 1 and either 2 or 3 [or both]) Inclusion/Exclusion Criteria: Major EXCLUSION
      CRITERIA - FEMALE1) other uncorrected endocrinopathy- hyperprolactinemia, hyper- or
      hypothyroidism, congenital adrenal hyperplasia2) presence of overt diabetes or impaired
      glucose tolerance3) alterations in hepatic or renal function4) use of hormonal medications,
      insulin sensitizers or medications that interfere with carbohydrate metabolism for at least 8
      weeks5) Any medical condition which, in the judgment of the investigator may interfere with
      the absorption, distribution, metabolism or excretion of the drug6) Simultaneous
      participation in another clinical trial7) Known active substance abuse including tobacco and
      alcohol. (> 10 cigarettes/day)8) Refusal or inability to comply with protocol9) patient
      desiring pregnancy, pregnant, or breastfeeding Study Design: Balanced randomized parallel
      group clinical study with 3 treatment arms: metformin (1000 mg BID); exenatide (10 mcg BID)
      or combined (metformin 1000 mg BID; exenatide 10 mcg BID) therapy for 24 weeks.

      Efficacy Measures: Primary- Menstrual Cyclicity ( # menses/ 24 weeks)Secondary-BMI, WHR, FAI
      (T/SHBG), DHEAS, lipids, insulin resistance-(HOMA and composite insulin sensitivity index [
      SIOGTT), and pancreatic ß-cell function (corrected insulin response [CIRgp] and insulinogenic
      index [IGI] ).

      Safety: For safety, all subjects who enter the study are evaluable. Subjects will be
      monitored for safety by assessment of adverse events, physical exams, vital signs and
      laboratory values.

      Statistical methods/analysis: The measurement of menstrual frequency involves nominal data (
      patients with/without regular cycles pre vs post-treatment and will be analyzed using the
      McNemar test (complex chi square for paired data). For all other analyses, in which the data
      are interval, parameters, such as androgens, lipids, insulin sensitivity, etc. will be
      evaluated using a SS/Treatment x Trials (pre/post) analyses of variance (ANOVA). This
      repeated measures design will allow us to determine if each of the treatment drugs had an
      effect and if they are significantly different from each other while controlling for
      individual patient differences Study Drug Regimens: Exenatide5 ug bid - 4 weeks10 ug bid - 20
      weeks (end of study)Metformin500 mg qd 2 weeks500 mg bid 2 weeks 500 mg am, 1000 mg pm- 2
      weeks1000 mg bid -18 weeks (end study) Exenatide plus MetforminExenatide- 5 ug bid-4
      weeksMetformin 500 qd for 2 weeks, 500 mg bid 2 weeksExenatide- 10 ug -20 weeks (to end of
      study)Metformin-500 mg am, 1000 mg pm- 2 weeks - 1000 bid for 18 weeks (end of study)**
      Metformin may be adjusted at the discretion of the physician to a level that is tolerable in
      patients who cannot tolerate the full dose of metformin in combination with exenatide
      (combination therapy only )
    

Intervention name(s): metformin, exenatide or combined (metformin & exenatide )
Intervention type(s): Drug
Intervention MeSH terms: Metformin; Exenatide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: menstrual cyclicity; insulin resistance; body fat distribution; pancreatic ß-cell function; inflammatory markers; liver function tests