Saxagliptin + Metformin Compared to Saxagliptin or Metformin Monotherapy in PCOS Women With Impaired Glucose Homeostasis
Condition: Polycystic Ovary Syndrome; Disorder of Glucose Regulation
MeSH terms: Polycystic Ovary Syndrome
Intervention: Metformin XR; Saxagliptin; Saxagliptin-Metformin XR
Intervention description: Start 2 pills (2 pills of 500 mg =1000mg XR) for 3 weeks
Increase to 4 pills as tolerated (4 pills of 500 mg XR =2000 mg XR) for remainder of study; Start 1 pill (5 mg)) for 3 weeks
Remain at 1 pill (5mg dose) for remainder of study; Start 1 pill (2.5 mg/ 1000mg XR) for 3 weeks
Increase to 2 pills as tolerated (5mg/2000 mg XR) for remainder of study
Intervention MeSH terms: Metformin; Saxagliptin; Biguanides; Dipeptidyl-Peptidase IV Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Enrollment: 38.0
Sex: Female
Minimum age: 18 Years
Maximum age: 42 Years
Healthy volunteers: No
Keywords: PCOS; IGT; DPP-4 inhibitor

Summary:

      The objective of the present proposal is to compare the clinical, endocrine and metabolic
      effects of therapy with combination saxagliptin and metformin to saxagliptin and metformin
      monotherapy in women with PCOS and prediabetic hyperglycemia (IFG, IGT or IFG/IGT).
      Saxagliptin is an oral dipeptidyl peptidase IV (DPP-4) inhibitor whose mechanism of action is
      to prolong the duration of blood glucagon-like peptide (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) levels by inhibiting their degradation and thereby
      augmenting insulin secretion. This study will serve as a pilot investigation to open
      perspectives for future studies to explore the potential of combining anti-diabetic drugs
      with different mechanisms of action in in patients with PCOS and impaired glucose regulation
      (IGR), especially ones for whom standard treatment with metformin is less effective.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females 18 years to 42 years of age with polycystic ovary syndrome(NIH PCOS criteria)
             with prediabetic hyperglycemia determined by an 75 gram oral glucose tolerance test
             (OGTT). Study subjects will be inclusive of PCOS women with impaired fasting glucose
             (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT).

          -  Written consent for participation in the study

        Exclusion Criteria:

          -  Presence of significant systemic disease, heart problems including congestive heart
             failure, history of pancreatitis, or diabetes mellitus (Type 1 or 2)

          -  Any hepatic diseases in the past (viral hepatitis, toxic hepatic damage, jaundice of
             unknown etiology), gallstones, abnormal liver function tests or renal impairment
             (elevated serum creatinine levels or abnormal creatinine clearance)

          -  Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital
             adrenal hyperplasia or hyperprolactinemia

          -  Significantly elevated triglyceride levels (fasting triglyceride > 400 mg %)

          -  Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)

          -  Use of hormonal medications, drugs known to affect gastrointestinal motility,
             lipid-lowering (statins, etc.) and/or anti-obesity drugs or medications that interfere
             with carbohydrate metabolism (such as isotretinoin, hormonal contraceptives,
             gonadotropin releasing hormone (GnRH) analogues, glucocorticoids, anabolic steroids,
             C-19 progestins) for at least 8 weeks. Use of anti-androgens that act peripherally to
             reduce hirsutism such as 5-alpha reductase inhibitors (finasteride, spironolactone,
             flutamide) for at least 4 weeks

          -  Prior history of a malignant disease requiring chemotherapy

          -  Known hypersensitivity or contraindications to use of insulin sensitizers such as
             metformin or thiazolidinediones

          -  History of hypersensitivity reaction to saxagliptin or other DPP-4 inhibitors (e.g.
             anaphylaxis, angioedema, exfoliative skin conditions)

          -  Current use of metformin, thiazolidinediones, glucagon-like peptide -1 receptor
             agonists, DPP-4 inhibitors, or weight loss medications (prescription or OTC) Patients
             must stop use of insulin sensitizers or antidiabetic medicines such as metformin for
             at least 4 weeks or thiazolidinediones, GLP1 agonists or DPPIV inhibitors for 8 weeks.

          -  Prior use of medication to treat diabetes except gestational diabetes

          -  Use of drugs known to exacerbate glucose tolerance

          -  Eating disorders (anorexia, bulimia) or gastrointestinal disorders

          -  Suspected pregnancy (documented negative serum pregnancy test), desiring pregnancy
             during the study treatment interval, breastfeeding, or known pregnancy in last 2
             months

          -  Active or prior history of substance abuse (smoke or tobacco use within past 3 years)
             or significant intake of alcohol or history of alcoholism

          -  Patient not willing to use adequate barrier contraception during study period (unless
             sterilized or have an IUD).

          -  Debilitating psychiatric disorder such as psychosis or neurological condition that
             might confound outcome variables

          -  Inability or refusal to comply with protocol

          -  Not currently participating or having participated in an experimental drug study in
             previous three months