Semaglutide for prevention of type 2 diabetes in women with postpartum prediabetes after gestational diabetes: protocol for a Belgian multicentre double-blind randomised placebo-controlled trial.

INTRODUCTION: Women with postpartum pre-diabetes following gestational diabetes mellitus (GDM) are at particularly high risk of developing type 2 diabetes mellitus (T2DM). While the implementation of effective lifestyle interventions in the early postpartum period is often difficult and has in general limited efficacy to prevent T2DM after GDM, effective preventive strategies, including medical therapies, are needed in this population. The 'semaglutide for the treatment of pre-diabetes in women with prior gestational diabetes (SERENA) study' aims to evaluate the efficacy, safety and cost-effectiveness of semaglutide in preventing progression to T2DM during the early postpartum period. METHODS AND ANALYSIS: SERENA is a Belgian multicentre, double-blind randomised controlled trial conducted in 13 hospitals. A total of 252 women with a recent history of GDM and postpartum pre-diabetes will be randomised in a 1:1 ratio to receive once-weekly subcutaneous injections of semaglutide 1 mg or placebo in addition to standardised lifestyle intervention. Randomisation is stratified by body mass index at early postpartum assessment (<25, 25-29.9 and ≥30 kg/m²). Participants will be treated for up to 160 weeks (3 years), with a total follow-up period of up to 184 weeks (3 years and 6 months). Study visits are scheduled every 6 months and include blood sampling, clinical examinations and completion of self-administered questionnaires. The primary outcome is the development of T2DM based on the American Diabetes Association criteria. Secondary outcomes include need for diabetes rescue therapy, regression to normoglycaemia, weight loss, insulin sensitivity, beta-cell function, cardiometabolic risk profile, patient-reported outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: The study was approved by the Federal Agency for Medicines and Health Products and the relevant Ethics Committees (2022-502082-22-00) (S66967). Recruitment started in September 2023. Study results will be disseminated through peer-reviewed publications and presentations at scientific conferences. Individual participant data will be made available on reasonable request after study completion, database lock, unblinding and publication of the primary results, subject to applicable ethical, legal and data protection requirements. TRIAL REGISTRATION NUMBER: NCT05569772.