Intervention: Kombiglyze
Trial phase: Phase 3
SMILES: CN(C)C(=N)N=C(N)N.N#CC1CC2CC2N1C(=O)C(N)C12CC3CC(CC(O)(C3)C1)C2
Sex: Female
Age groups: Adult
Healthy volunteers: No
Participants at risk: 13
Group description: Saxagliptin-Metformin XR (combination pill)

5mg Saxagliptin/2000 mg Metformin XR QD for 16 weeks

Saxagliptin-Metformin XR: 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
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