Precision Obesity Medicine: Genetic Prediction of Response to GLP-1/GIP Agonists. (Diagenix)
Prediction of Response to GLP-1/GIP Receptor Agonists in Obesity Using Genetic Risk Score and SNP Profiling: A Prospective Cohort Study.
Obesity is a chronic multifactorial disease with a strong genetic component. Although glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, such as tirzepatide, are highly effective treatments for obesity, substantial inter-individual variability in weight loss response remains. Genetic factors may contribute to these differences in treatment outcomes.
The aim of this prospective cohort study is to investigate whether a Genetic Risk Score (GRS) and selected obesity-related single nucleotide polymorphisms (SNPs) can predict weight loss response to semaglutide or tirzepatide in adults with obesity. Participants initiating treatment with either medication will undergo clinical, biochemical, and genetic assessment at baseline and will be followed for six months. The study will evaluate the association between genetic markers and treatment response and develop predictive models integrating genetic and clinical variables. The findings may contribute to the development of personalized treatment strategies for obesity.
Обзор исследования
Статус
Вмешательство/лечение
Подробное описание
Obesity is a chronic disease resulting from complex interactions between genetic, environmental, and behavioral factors. Genetic influences account for a substantial proportion of obesity susceptibility, with heritability estimates ranging from 40% to 75%. Genome-wide association studies have identified numerous genetic variants associated with body mass index, appetite regulation, energy homeostasis, and metabolic function.
Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GIP/GLP-1 receptor agonists have significantly improved the pharmacological management of obesity. Semaglutide and tirzepatide produce clinically meaningful weight reduction and improvement in metabolic outcomes. However, treatment response varies considerably among individuals, and the factors underlying this variability are not fully understood.
Genetic Risk Scores (GRS), which combine the effects of multiple obesity-related genetic variants, have emerged as potential tools for predicting disease risk and therapeutic response. Their role in predicting response to anti-obesity pharmacotherapy remains largely unexplored.
This prospective observational cohort study aims to evaluate whether a GRS and selected obesity-related single nucleotide polymorphisms (SNPs) can predict weight loss response to semaglutide or tirzepatide in adults with obesity.
Eligible participants initiating treatment with semaglutide or tirzepatide will be consecutively recruited and followed for six months. At baseline, demographic, clinical, anthropometric, biochemical, and genetic data will be collected. Approximately 18 obesity-related SNPs, including variants in genes involved in appetite regulation, energy balance, and glucose metabolism, will be analyzed. An additive Genetic Risk Score will be calculated based on the cumulative number of risk alleles.
The primary outcome will be percentage weight loss at six months. Participants will subsequently be classified according to treatment response. Associations between genetic markers, GRS categories, and treatment outcomes will be evaluated using multivariable regression models. Receiver operating characteristic (ROC) curve analyses will be performed to assess the predictive performance of genetic and combined genetic-clinical models.
The study is expected to identify genetic predictors of response to GLP-1/GIP receptor agonist therapy and contribute to the development of precision medicine approaches in obesity management. Improved prediction of treatment response may facilitate individualized therapeutic selection, optimize clinical outcomes, and reduce the trial-and-error approach currently used in obesity pharmacotherapy.
Тип исследования
Регистрация (Оцененный)
Контакты и местонахождение
Контакты исследования
- Имя: Maria P Yavropoulou, MD, MSc, PDH
- Номер телефона: +306936159517
- Электронная почта: myavropoulou@med.uoa.gr
Учебное резервное копирование контактов
- Имя: Maria Evangelia Koloutsou, MD
- Номер телефона: +306986606272
- Электронная почта: mkoloutsou@med.uoa.gr
Места учебы
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Athens, Греция, 11527
- Рекрутинг
- Laiko General Hospital, Athens
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Контакт:
- Maria Evangelia Koloutsou, MD
- Номер телефона: +306986606272
- Электронная почта: mkoloutsou@med.uoa.gr
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Контакт:
- Maria Yavropoulou, MD, MSc, PHD
- Номер телефона: +306936159517
- Электронная почта: myavropoulou@med.uoa.gr
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Главный следователь:
- Nikolaos Tentolouris, Prof
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Младший исследователь:
- Maria Evangelia Koloutsou, MD
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Метод выборки
Исследуемая популяция
Описание
Inclusion Criteria:
- Age ≥18 years
- BMI ≥40 kg/m² or ≥37 kg/m² with comorbidities
- Initiation of semaglutide or tirzepatide
Exclusion Criteria:
- Prior bariatric surgery
- Secondary causes of obesity
- Active malignancy
- Chronic pancreatitis
- Family history of medullary thyroid carcinoma
Учебный план
Как устроено исследование?
Детали дизайна
Когорты и вмешательства
Группа / когорта |
Вмешательство/лечение |
|---|---|
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Semaglutide or Tirzepatide
Adults with obesity initiating treatment with semaglutide or tirzepatide as part of routine clinical care.
Participants are followed prospectively for 6 months to evaluate weight loss response and its association with genetic risk score.
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Adults with obesity initiating treatment with semaglutide or tirzepatide as part of routine clinical care.
Participants are followed prospectively for 6 months to evaluate weight loss response and its association with genetic risk score.
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Percentage weight loss at 6 months
Временное ограничение: 6 months
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Percentage change in body weight from baseline to 6 months following treatment with semaglutide or tirzepatide.
The association between weight loss response and genetic risk score (GRS) as well as obesity-related single nucleotide polymorphisms (SNPs) will be evaluated.
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6 months
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Соавторы и исследователи
Публикации и полезные ссылки
Общие публикации
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Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Патологические процессы
- Расстройства питания
- Атрибуты болезни
- Переедание
- Масса тела
- Избыточный вес
- Восприимчивость к болезням
- Генетическая предрасположенность к заболеваниям
- Патологические состояния, признаки и симптомы
- Пищевые и метаболические заболевания
- Признаки и симптомы
- Оценка генетического риска
- Ожирение
- Аминокислоты, пептиды и белки
- Белки
- Глюкагоноподобный рецептор пептида-1
- Глюкагоноподобные пептидные рецепторы
- Рецепторы, G-белок связаны
- Рецепторы, клеточная поверхность
- Мембранные белки
- Рецепторы, желудочно -кишечный гормон
- Рецепторы, пептид
- Тирзепатид
- полуглутид
Другие идентификационные номера исследования
- 5002
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .