Real-life Evaluation of WEGOVY (Semaglutide) Treatment in Adults With Monogenic Obesity (ObGeSema) (ObGeSema)

A Multicenter Pharmacoepidemiological Cohort on Real Life Use of WEGOVY (Semaglutide) in Obese Patients With Monogenic Obesity

Rare genetic forms of obesity, so called monogenic obesity are linked to alteration in energy balance involving hypothalamic pathways.

More than 60 genes encoding for proteins located in the hypothalamic leptin/melanocortin pathway have been described in the French National Protocol for Diagnostic and Care (PNDS).

The natural history of monogenic obesity is characterized by an early onset in childhood, with a major increase in weight in adolescence and young adulthood. The worsening of obesity exposes these patients to severe complications.

Severe obesity and eating disorders have a major impact on the quality of life of the person but also of the family and caregivers. Clinical management is complex and requires comprehensive, specialized and multidisciplinary management. But the usual lifestyle approaches have so far shown disappointing results, similarly to bariatric surgery which leads to a more frequent weight regain in the situation of monogenic obesity, justifying new approaches.

In this context, evaluating the response to treatment in the particular condition of monogenic obesity is crucial to propose therapeutic options as early as possible to limit weight evolution and its complications.

GLP-1 (glucagon-like peptide 1) based innovative therapies have recently emerged as a promising option for treatment of obesity and its complications. This is the case for Semaglutide 2.4mg/week (WEGOVY®), developed by Novo Nordisk. However, there is a lack of data to confirm that semaglutide could be also effective in monogenic obesity.

The hypothesis in this study is that treatment with Semaglutide 2.4mg/week (WEGOVY®) could be as effective in monogenic obesities as in common obesity.

Study Overview

• Status: Recruiting
• Conditions: Monogenic Obesity

Detailed Description

Rare genetic forms of obesity, so called monogenic obesity are linked to alteration in energy balance involving hypothalamic pathways. More than 60 genes encoding for proteins located in the hypothalamic leptin/melanocortin pathway have been described in the French National Protocol for Diagnostic and Care (PNDS).

The natural history of monogenic obesity is characterized by an early onset in childhood, with a major increase in weight in adolescence and young adulthood. The worsening of obesity exposes these patients to severe complications. Severe obesity and eating disorders have a major impact on the quality of life of the person but also of the family and caregivers. Clinical management is complex and requires comprehensive, specialized and multidisciplinary management. But the usual lifestyle approaches have so far shown disappointing results, similarly to bariatric surgery which leads to a more frequent weight regain in the situation of monogenic obesity, justifying new approaches.

In this context, evaluating the response to treatment in the particular condition of monogenic obesity is crucial to propose therapeutic options as early as possible to limit weight evolution and its complications.

GLP-1 (glucagon-like peptide 1) based innovative therapies have recently emerged as a promising option for treatment of obesity and its complications. This is the case for Semaglutide 2.4mg/week (WEGOVY®), developed by Novo Nordisk. However, there is a lack of data to confirm that semaglutide could be also effective in monogenic obesity.

The hypothesis in this study is that treatment with Semaglutide 2.4mg/week (WEGOVY®) could be as effective in monogenic obesities as in common obesity.

This study is a multicenter study which involves French largest Specialized Obesity Centers (CSO) (among which the APHP coordinating center) All adult patients with a genetic diagnosis of obesity to whom Wegovy is proposed, as part of the WEGOVY® early access and/or commercialization, or for whom Wegovy has already been initiated will be proposed to participate to the study. This also includes any patient having initiated the treatment and already having interrupted it, for any reason.

After the information has been done, the patient or guardian gives to the physician their oral non-opposition for the study that is recorded in the medical records.

This study will take advantage of WEGOVY's pre-marketing, early access authorisation and/or commercialization in France to set up a longitudinal follow-up of patients with monogenic obesity receiving Semaglutide.

Patients already treated with semaglutide at the time of study start (i.e. patients having initiated the treatment in the Early Access programme) will be included and followed-up, whereas inclusion and prospective follow-up of newly treated patients will only begin when Semaglutide becomes officially available.

The aim of the ObGeSema project is to set up a cohort composed of patients (1) having already initiated a treatment and (2) newly treated by Semaglutide in 14 Specialized Obesity Centres (CSOs) and describe their evolution over a 4 year follow-up.

• Study Type: Observational
• Enrollment (Estimated): 175

Contacts and Locations

• Study Contact: Name: Christine POITOU-BERNERT, MD,PhD; Phone Number: +33(0)142175771; Email: christine.poitou-bernert@aphp.fr
• Study Contact Backup: Name: Sarra POCHON; Phone Number: +33(0)142167574; Email: sarra.pochon@aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Not yet recruiting
    • Centre de référence Syndrome de Prader-Willi et autres obésités avec troubles du comportement alimentaire (PRADORT). Service de Nutrition, GH Pitié-Salpêtrière, APHP
    • Contact: Emilie GUILLON; Email: emilie.guillon-ext@aphp.fr
    • Contact: Sarra POCHON; Phone Number: +33(1)42167574; Email: sarra.pochon@aphp.fr
  • Paris, France, 75013
    • Recruiting
    • CHU Pitié Salpêtrière - APHP
    • Contact: Christine POITOU-BERNERT, MD, PhD; Phone Number: +33(0)142175771
    • Principal Investigator: Christine POITOU-BERNERT, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults (≥18 years) with monogenic obesity due to a pathogenic variant already treated or with the physician's decision to initiate treatment with Semaglutide 2.4mg/week (WEGOVY®) in the standard care. Patients under legal protection and State Medical Assistance (AME) will be included.

Description

Inclusion Criteria:

• Adult Patients (≥18 years)having already initiated a treatment with SEMAGLUTIDE (WEGOVY®) or with a physician's decision to initiate treatment in the standard care in the near future. All patients having initiated a treatment will be proposed to participate, including those having already stopped the treatment at the time of study initiation.
• Confirmation of monogenic obesity, as practiced in clinical routine, by the presence of a pathogenic or likely pathogenic variant in a gene with leptin-melanocortin pathway described in PNDS (https://www.has-sante.fr/jcms/p_3280217/fr/generique-obesites-de-causes-rares)
• Patients duly informed and not objecting to participate in the study
• Patients affiliated to a social security scheme or State Medical Assistance (AME).

Exclusion Criteria:

• Pregnant and breastfeeding women

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in weight and Body Mass Index (BMI)	Percentage of subjects with a change in weight and Body Mass Index (BMI).Weight will be measured at initiation and at 12 months of the Wegovy treatment	From baseline (T0) to T12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in weight and Body Mass Index (BMI)	Percentage of subjects with a change in weight and Body Mass Index (BMI). Weight will be measured at initiation of the Wegovy treatment and at each visit	From baseline (T0) to 6 and/or 24 and/or 36 and/or 48 and/or 60 months
Reduction of body weight equal to or above 5%	Percentage of subjects achieving a reduction of body weight equal to or above 5%(number of subjects with a % of body weight changes > -5%)X100/ number of the total subject	From baseline (T0) to 6 and/or 12 and/or 24 and/or 36 and/or 48 and/or 60 months
Change in Hunger score	Number and percentage of subjects with change in Hunger score	From baseline (T0) to 12 and/or 24 and/or 36 and/or 48 and/or 60 months
Change in eating behaviour measured by Food Craving questionnaire	Number and percentage of subjects with change in Food Craving scale	From baseline (T0) to 12 months
Change in eating behaviour measured by the Binge Eating Scale (BES)	Number and percentage of subjects with change in Binge Eating Scale (BES)	From baseline (T0) to 12 months
Change in eating behaviour measured by the Dutch Eating Behaviour Questionnaire (DEBQ)	Number and percentage of subjects with change in Dutch Eating Behaviour Questionnaire (DEBQ)	From baseline (T0) to 12 months
Change in eating behaviour measured by the Dykens questionnaire	Number and percentage of subjects with change in Hyperphagia score with the Dykens questionnaire for intellectual disability	From baseline (T0) to 12 months
Change in eating behaviour measured by the Child Eating Behaviour Questionnaire (CEBQ)	Number and percentage of subjects with change in the Child Eating Behaviour Questionnaire (CEBQ) for intellectual disability	From baseline (T0) to 12 months
Change in the International physical activity questionnaire (IPAQ - short form)	Number and percentage of subjects with change of the International physical activity	From baseline (T0) to 12 months
Change in Digestive disorders (GIQLI )	Number and percentage of subjects with change in Digestive disorders (GIQLI ). Digestive disorders are measured by the Gastrointestinal Quality of Life Index (GIQLI)	From baseline (T0) to 12 and/or 24 and/or 36 and/or 48 and/or 60 months
Change in sleep disorder (MCTQ score)	Number and percentage of subjects with Change in sleep disorder. Sleep disorder is measured with the Micro Munich Chronotype Questionnaire (MCTQ)	From baseline (T0) to 12 months
Change in score of quality of life scores (patient and parents)	Number and percentage of subjects with change in score of quality of life scores .Quality of life is measured with the Impact of Weight on Quality of Life-Lite scale (IWQOL-Lite)	From baseline (T0) to 12 months
Change in anxiety and depression score	Number and percent of subjects with change in anxiety and depression score. Anxiety and depression is measured with the Hospital Anxiety and Depression scale (HAD)	From baseline (T0) to 12 and/or 24 and/or 36 and/or 48 and/or 60 months
Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	Number of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	From baseline (T0) to 6 and/or 12 and/or 24 and/or 36 and/or 48 and/or 60 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Christine POITOU-BERNERT, MD,PhD, Assistance Publique - Hôpitaux de Paris; Study Director: Béatrice DUBERN, MD,PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: April 11, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 23, 2024

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: August 6, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Semaglutide; Monogenic obesity; WEGOVY
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity
• Other Study ID Numbers: APHP230441; IDRCB : 2023-A02003-42 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodological sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No