DUGi

Effect of semaglutide combined with lifestyle intervention on ovulation rate, androgen excess and metabolic outcomes in adolescent and young adult women with polycystic ovary syndrome: an open-label randomized clinical trial

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@10256@@28601

BACKGROUND Polycystic Ovary Syndrome (PCOS) is the most prevalent chronic endocrine-metabolic disorder of Adolescents and Young Adult Women (AYAs). It is characterized by hyperandrogenism and menstrual irregularities. It also has an elevated prevalence of obesity, insulin resistance, lifelong co-morbidities, and it is the leading cause of anovulatory subfertility. JUSTIFICATION There is no EMA/FDA-approved pharmacological therapy for AYAs with PCOS, so existing treatments are prescribed off-label. Lifestyle intervention and metformin, partially improve the underlying pathophysiology but with limited effect, while others, such as oral contraceptives and antiandrogens, relieve symptoms. Semaglutide could address the core pathophysiology by reducing central and hepatic fat, improving insulin resistance, and lowering androgen levels, potentially restoring ovulatory function, and improving metabolic and hormonal profiles. OBJECTIVES The Primary objective of this clinical trial is to evaluate whether the combination of Semaglutide and Lifestyle Intervention is superior to Lifestyle Intervention alone in normalizing ovulation rate in AYAs with PCOS. Secondary objectives include regards of improve menstrual regularity, clinical and biochemical hyperandrogenism, metabolic disorders, health-related quality of life, and incidence of adverse effects. DESIGN This is a phase 2, randomized, open label, multicentre, 12-months clinical trial. PARTICIPANTS Participants will consist of 152 AYAs aged from 12 to 18 with PCOS. Informed consent will be obtained from parents, and from participants aged 18 years, prior to eligibility assessment based on the study´s inclusion and exclusion criteria. MAIN OUTCOME MEASURES Primary outcome: on treatment ovulation rate. Secondary outcomes: Menstrual Regularity, Modified Ferriman-Gallwey, Leeds Scale, Total Testosterone, Sex Hormone Binding Globulin, Free Androgen Index, HOMA-IR, Glucose Tolerance, Total Cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, BMI, Waist-to-hip ratio, quantification of hepato-visceral fat, ultra-sensitive C-reactive protein, Carotid Intima Media thickness, SF- 36, PCOSQ and safety variables. INTERVENTION AND METHODS Participants will be randomized 1:1 to receive either Semaglutide combined with Lifestyle Intervention or Lifestyle Intervention alone. Semaglutide will be administered onceweekly by subcutaneous injection with a dose-escalation schedule. Follow-up assessments will be conducted every three months. ANALYSIS Primary and secondary outcomes will be analysed using univariate, bivariate, and multivariate methods, adjusted for covariates. The main outcome, ovulation rate, will be evaluated with a multivariate rank-based test suitable for discrete quantitative variables. SETTING Multicentre: H. Josep Trueta, H. Sant Joan de Déu and H. Vall d’Hebron

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