SEMASEARCH, Retrospective/Prospective Cohort Nested at ATUc/AP2 WEGOVY®

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.


Eligibility Criteria:
Inclusion Criteria:

* Over 18 years of age
* Initial body mass index (BMI) ≥ 40 kg/m² (class III obesity or morbid obesity) in the presence of at least one weight related comorbidity factor:

  * Treated hypertension
  * Treated dyslipidemia
  * Established cardiovascular disease
  * Treated Sleep apnea syndrome
* Patient enrolled in ATUc/AP2 WEGOVY®SEMAGLUTIDE 2.4mg/wk in the 15 participating CSO
* Patient who was informed and did not object to participate in the study
* Patient enrolled in a social security scheme
* Pregnant or lactating women are excluded from the WEGOVY® ATUc/AP2. Effective contraception is required for women of childbearing potential to access WEGOVY® AP.
* Criteria for tagging, at baseline, patients according to the following subpopulation of interest: (the tag does not condition the inclusion of the patient in this cohort, it makes it possible to identify the subpopulations):

Patients with a history of bariatric surgery:

* 1 year or more after bariatric surgery (definitive technique or ring in place)
* Surgery failure defined by: i-Initial PEP \< 50% (including no weight gain) // ii- and/or weight regain \> 20% of the weight lost compared to the postoperative weight nadir

Patients with severe eating disorder, binge eating disorder : To be defined by the clinician according to the DSM5 definition of binge eating disorder

* Recurrent occurrence of binge eating, hyperphagic attack meeting the following two characteristics: i- Absorption, in a limited period of time, of a much greater amount of food than most people would absorb in a similar period of time and under the same circumstances // ii- Feeling of loss of control over eating behaviour during binge eating:
* Binge eating is associated with three (or more) of the following characteristics:i- Eat much faster than normal. ii- Eat until you experience a painful feeling of abdominal distension.// Iii- Eating large amounts of food in the absence of a physical feeling of hunger.// Iv- Eating alone because you are embarrassed about the amount of food you absorb.// V- Feeling disgusted with yourself, depressed or very guilty after eating.
* Bulimic behavior is a source of marked suffering. d- Bulimic behavior occurs, on average, at least 1 day a week for 5 months.
* Bulimic behaviour is not associated with the regular use of inappropriate compensatory behaviours (e.g., vomiting or purgative, fasting, excessive physical exercise) and does not occur during anorexia nervosa or bulimia.

Patients with a rare form of monogenic or syndromic obesity OR psychomotor retardation All the situations described in the PNDS Obesity of rare causes: https://www.hassante.fr/jcms/p_3280217/fr/generique-obesites-de-causes-rares

* These are: i- hypothalamic lesional obesity such as craniopharyngiomas // ii- obesity of genetic origin.
* The most frequently encountered are: i-Prader-Willi // ii-BardetBiedl // iii Délétion16p11.2ouvariantSH2B1 // iv- Variants LEPR, POMC,PCSK1 et MC4R The list of genes is detailed in the link: https://docs.google.com/spreadsheets/d/1vQUcZna_vjpgVLLtylDKc1zIVRNvoSPOVlTsixUdT Wg/edit# gid=0.

Sarcopenic elderly patients:

* Age \> 60
* Pathological chair lift test (gets up 5 times from a chair without standing in + 15 seconds)

Patients with extreme obesity:

* IMC\>60kg/m²

Patients with iatrogenic obesity induced by psychotropic drugs:

* Presence of one of the following treatments at the patient's baseline: i- Antidepressants:1- selective serotonin reuptake inhibitors (SSRIs) / 2-Serotonin reuptake inhibitors and norepinephrine (the "double-action") / 3-tricyclic antidepressants (TCAs) / 4-"other antidepressants" : a- Thymoregulatory drugs: Lithium, Valproate, Gabapentine, Carbamazépine, Lamotrigine, Topiramate OR b- Antipsychotics (i- Typical (= first generation): chlorpromazine, levomépromazine, cyamémazine, halopéridol, dropéridol, sulpiride, amisulpride // ii- Atypical (= second generation): zuclopenthixol, clozapine, cloxapine, olanzapine, risperidone, quetiapine)

Non-specific patient (patient who does not have a criterion that can be classified into one of the subpopulations)

Patient NOT tagged (Tag not done or insufficient elements to classify the patient)

Exclusion Criteria:

* Criteria for non-inclusion in the WEGOVY® ATUc/AP2
* Vulnerable patient (person under guardianship or curatorship, or deprived of liberty by a judicial or administrative decision).
* Pregnant women or breastfeeding