Semaglutide vs Metformin in Polycystic Ovary Syndrome (PCOS)

Inclusion Criteria:

1. Willingness and ability to provide signed informed consent prior to any trial activity.
2. Women, aged 18-45 years (inclusive), with confirmed diagnosis of PCOS based on Rotterdam criteria \[12\].
3. Body mass index ≥30 kg/m2
4. Negative pregnancy test during screening visit and agree to use barrier contraception during the study period.
5. Participants from all ethnicities who are English speakers

Exclusion Criteria:

1. Non-classical 21-hydroxylase deficiency, hyperprolactinaemia, Cushing's disease, and androgen-secreting tumours will be excluded by appropriate tests.
2. Confirmed type 2 diabetes and type 1 diabetes.
3. Pregnancy, breastfeeding or intends to become pregnant.
4. Subjects who are on any of the following medications within 3 months of screening:

   * Metformin or other insulin-sensitizing medications (e.g. pioglitazone)
   * Hormonal contraceptives (e.g. birth control pills, hormone-releasing implants. Locally acting hormone - containing IUD such as Mirena coil is permitted).
   * Anti-androgens (e.g., spironolactone, flutamide, finasteride, etc.)
   * Clomiphene citrate or oestrogen modulators such as letrozole
   * GnRH modulators such as leuprolide
   * Minoxidil
5. Have been involved in another medicinal trial (CTIMP) within the past four weeks.
6. Presence or history of neoplasm within 5 years prior to screening. Basal skin carcinoma is allowed.
7. History of pancreatitis
8. Any regular medications that would affect weight management (such as steroids)
9. Any contraindications for treatment with semaglutide.
10. Participants under 18 years
11. Participants who cannot adequately understand verbal and / or written explanations given in English.
12. Confirmed excessive and compulsive drinking of alcohol i.e., alcohol abuse as determined from GP medical notes by the Fast Alcohol Screening Test (FAST) or history of previous alcohol abuse.
13. Moderate to severe renal impairment (creatinine clearance \[CrCl\] ≤ 60 ml/min or estimated glomerular filtration rate \[eGFR\] ≤ 60 ml/min/1.73 m2.
14. Severe hepatic insufficiency / and or significant abnormal liver function defines as aspartate aminotransferase (AST) \>3x upper limit of normal (ULN) and / or alanine aminotransferase (ALT) \> 3ULN.
15. History of a major surgical procedure involving the stomach or small intestine which could affect absorption as judged by the investigator.
16. Have severe and enduring mental health problems.
17. Personal or first-degree relative history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid cancer (MTC).
18. Clinical or radiological evidence of thyroid nodules.
19. Any contraindication to the administration of metformin.