EQW, DAPA, EQW/DAPA, DAPA/MET ER and PHEN/TPM ER in Obese Women With PolycysticOvary Syndrome (PCOS)

Inclusion Criteria:

1. Non-diabetic women (18-45 years)
2. PCOS- NIH criteria hyperandrogenism and irregular menses
3. Obese class I, II, and III (BMI \>30\<45)
4. Willing to use effective contraception consistently during therapy which is defined as:

   1. an intrauterine device, tubal sterilization, or male partner vasectomy, or
   2. combination of two barrier methods with one being male condom.
5. Written consent for participation in the study

Exclusion Criteria:

1. Presence of significant systemic disease, heart problems including congestive heart failure, unstable angina or acute myocardial infarction, current infectious liver disease, acute stroke or transient ischemic attacks, history of pancreatitis, or diabetes mellitus (Type 1 or 2)
2. Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or significant abnormal liver function tests defined as aspartate aminotransferase (AST) \>3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) \>3x ULN
3. Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women, or estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease. Patients with a history of nephrolithiasis are also excluded due to increased association with kidney stone formation.
4. Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia
5. Significantly elevated triglyceride levels (fasting triglyceride \> 400 mg/dL)
6. Untreated or poorly controlled hypertension (sitting blood pressure \> 160/95 mm Hg)
7. Use of hormonal medications, lipid-lowering (statins, etc.), anti-obesity drugs or weight loss medications (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, hormonal contraceptives, gonadotropin-releasing hormone agonists, glucocorticoids, anabolic steroids, C-19 progestins) stopped for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finasteride, spironolactone, flutamide) stopped for at least 4 weeks
8. Prior history of a malignant disease requiring chemotherapy
9. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status
10. History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit.
11. Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions
12. Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide, liraglutide)
13. Use of metformin, thiazolidinediones, GLP-1 receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, SGLT2 inhibitors stopped for at least 4 weeks.
14. Prior use of medication to treat diabetes except gestational diabetes
15. Eating disorders (anorexia, bulimia) or gastrointestinal disorders
16. Suspected pregnancy (documented negative serum pregnancy test), desiring pregnancy in next 6 months, breastfeeding, or known pregnancy in last 2 months
17. Active or prior history of substance abuse (smoke or tobacco use within past 3 years) or significant intake of alcohol
18. Having a history of bariatric surgery
19. Patient not willing to use two barrier method contraception during study period (unless sterilized or have an IUD)
20. Patients with glaucoma or history of increased intraocular pressure, or use of any medications to treat increased intraocular pressure
21. Debilitating psychiatric disorder such as psychosis or neurological condition that might confound outcome variables. Patients with a history of bipolar disorder or psychosis, greater than one lifetime, episode of major depression, current depression of moderate or greater severity (PHQ-9score of 10 or more), presence or history of suicidal behavior or ideation with some intent to act on it, or antidepressant use that has not been stable for at least 3 months will also be excluded.
22. Inability or refusal to comply with protocol
23. Current participation or participation in an experimental drug study in previous three months

    \-