The aim of the SEMASEARCH project is therefore to constitute a retrospective cohort, from the available data on patients already included in the ATUc/AP2, and prospective, on new patients who will initiate treatment according to the AP2 PUT, of 15 Specialized Obesity Centers in order to describe the effect of WEGOVY® treatment in this population. Thanks to a high phenotyping, subpopulations of interest will be identified to know the specifics of the effect of the treatment in these subgroups of interest. Secondary analyses will aim to look for clinical or biological biomarkers of success in the weight response to WEGOVY® in the entire prospective cohort, but also in specific subpopulations.

In summary, the analysis of the entire SEMASEARCH cohort and sub-populations of interest will be based on a complete clinical phenotyping of patients (included in retrospective and prospective studies), completed by ad hoc questionnaires and associated with biological markers (prospective) partly collected within the framework of the WEGOVY® AP (glycaemia, hepatic assessment, lipid assessment ) and partly from a biobank to test specific hypotheses (predictive role of leptin sensitivity, insulin sensitivity level, plasma level of endocannabinoids, etc.).

In addition, approaches using artificial intelligence (AI), notably machine learning, will make it possible to determine the variables or combination of variables that are most predictive of the weight response to treatment with WEGOVY® in the largest population. Indeed, individual weight loss in response to weight loss strategies is highly variable, whether purely related to lifestyle changes or pharmacological. Well-known factors associated with the ability to lose weight include adherence to lifestyle change, gender, age and specific medications. However, after controlling for these factors, differences in weight loss appear to persist in response to different interventions including pharmacological ones. Adaptation to energy deficit involves complex feedback mechanisms, and inter-individual differences are likely to arise from a range of poorly defined factors. Thus, a better understanding of the factors involved in inter-individual variability in response to WEGOVY® will help guide more personalised approaches to the management of these patients. AI techniques will be used to determine which combination of clinical or biological variables are most predictive of weight response.

• Inclusion Criteria Male or female

Aged over 18 years

Patient included in the WEGOVY® ATU/AP program in one of the 14 participating CSOs: initial Body Mass Index (BMI) ≥ 40 kg/m² (Class III or morbid obesity) and presence of at least one weight-related comorbidity: treated hypertension, treated dyslipidemia, established cardiovascular disease, treated sleep apnea syndrome; and in the absence of therapeutic alternatives

Patient has been informed and has not objected to participation in the study

Patient affiliated with a French social security scheme

• Tagging Criteria to Identify Subpopulations of Interest (for classification purposes only - not a condition for inclusion)

  *1 Patients with a history of bariatric surgery:

  1. At least 1 year post-bariatric surgery (definitive technique or gastric band still in place)

  2. Defined as failure if:

     Initial %EWL < 50% (even without weight regain) and/or weight regain > 20% of lost weight compared to postoperative nadir

     *2 Patients with Binge Eating Disorder (BED):

     Defined by the clinician according to DSM-5 criteria for BED:

  a. Recurrent episodes of binge eating, characterized by both: Eating, in a discrete period of time, an amount of food that is definitely larger than what most individuals would eat in a similar time under similar circumstances A sense of lack of control over eating during the episode

  b. The binge eating episodes are associated with three (or more) of the following: Eating much more rapidly than normal Eating until uncomfortably full Eating large amounts of food when not physically hungry Eating alone due to embarrassment Feeling disgusted with oneself, depressed or guilty afterward

  c. Marked distress regarding binge eating

  d. The binge eating occurs, on average, at least once a week for 5 months

  e. The behavior is not associated with regular inappropriate compensatory behavior (e.g., purging, fasting, excessive exercise) and does not occur exclusively during anorexia nervosa or bulimia nervosa

  *3 Patients with rare monogenic or syndromic obesity: According to the French national guidelines (PNDS) for rare obesity causes: HAS website

  1. Includes:

     Hypothalamic (lesional) obesity, such as craniopharyngioma Genetic forms of obesity

  2. Most frequently encountered syndromes:

     Prader-Willi syndrome Bardet-Biedl syndrome 16p11.2 deletion or SH2B1 variant LEPR, POMC, PCSK1, and MC4R variants

     • 4 Older patients:

  1. Age > 60 years

     • 5 Patients with extreme obesity:

  a. BMI ≥ 60 kg/m²

  *6 Patients with obesity under psychotropic treatment:

Presence of one or more of the following treatments at baseline:

i. Antidepressants: Agomelatine, Amitriptyline, Citalopram, Clomipramine, Duloxetine, Escitalopram, Fluoxetine, Fluvoxamine, Imipramine, Iproniazid, Mianserin, Milnacipran, Mirtazapine, Moclobemide, Paroxetine, Sertraline, Tianeptine, Venlafaxine, Vortioxetine

ii. Antipsychotics: Amisulpride, Aripiprazole, Chlorpromazine, Clozapine, Cyamemazine, Flupenthixol, Fluphenazine, Haloperidol, Levomepromazine, Loxapine, Olanzapine, Pimozide, Pipamperone, Prochlorperazine, Quetiapine, Risperidone/Paliperidone, Sulpiride, Tiapride, Zuclopenthixol

iii. Mood stabilizers: Lithium carbonate, Carbamazepine, Lamotrigine, Oxcarbazepine, Sodium divalproate, Valpromide

iv. Psychostimulants: Methylphenidate

v. Anxiolytics: Antihistamines, anticonvulsants, or other anxiolytic agents

*7 Non-specific patients: Patients not meeting any of the above subpopulation criteria

- Exclusion Criteria

Pregnant or breastfeeding women

Persons under legal protection or guardianship

- Criteria for Early Study Withdrawal

Early withdrawal from the study will occur in the following cases:

The patient withdraws their non-opposition to participation

The patient discontinues treatment with WEGOVY® prematurely

All patients included in the 15 centers in the indication of AP2 : Adults with an initial body mass index ≥ 40 kg/m2 (class III obesity or morbid obesity) in the presence of at least one treated comorbidity (treated hypertension, treated dyslipidemia, treated OSAS, established CVD) and included in the ATUc/AP2 WEGOVY®.