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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Contacts et emplacements
Coordonnées de l'étude
- Nom: Maria P Yavropoulou, MD, MSc, PDH
- Numéro de téléphone: +306936159517
- E-mail: myavropoulou@med.uoa.gr
Sauvegarde des contacts de l'étude
- Nom: Maria Evangelia Koloutsou, MD
- Numéro de téléphone: +306986606272
- E-mail: mkoloutsou@med.uoa.gr
Lieux d'étude
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Athens, Grèce, 11527
- Recrutement
- Laiko General Hospital, Athens
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Contact:
- Maria Evangelia Koloutsou, MD
- Numéro de téléphone: +306986606272
- E-mail: mkoloutsou@med.uoa.gr
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Contact:
- Maria Yavropoulou, MD, MSc, PHD
- Numéro de téléphone: +306936159517
- E-mail: myavropoulou@med.uoa.gr
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Chercheur principal:
- Nikolaos Tentolouris, Prof
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Sous-enquêteur:
- Maria Evangelia Koloutsou, MD
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Méthode d'échantillonnage
Population étudiée
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
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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.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Percentage weight loss at 6 months
Délai: 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
|
Collaborateurs et enquêteurs
Publications et liens utiles
Publications générales
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LifeLines Cohort Study; Brennan EP, Choi M, Dastani Z, Drong AW, Eriksson P, Franco-Cereceda A, Gadin JR, Gharavi AG, Goddard ME, Handsaker RE, Huang J, Karpe F, Kathiresan S, Keildson S, Kiryluk K, Kubo M, Lee JY, Liang L, Lifton RP, Ma B, McCarroll SA, McKnight AJ, Min JL, Moffatt MF, Montgomery GW, Murabito JM, Nicholson G, Nyholt DR, Okada Y, Perry JRB, Dorajoo R, Reinmaa E, Salem RM, Sandholm N, Scott RA, Stolk L, Takahashi A, Tanaka T, van 't Hooft FM, Vinkhuyzen AAE, Westra HJ, Zheng W, Zondervan KT; ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium; Heath AC, Arveiler D, Bakker SJL, Beilby J, Bergman RN, Blangero J, Bovet P, Campbell H, Caulfield MJ, Cesana G, Chakravarti A, Chasman DI, Chines PS, Collins FS, Crawford DC, Cupples LA, Cusi D, Danesh J, de Faire U, den Ruijter HM, Dominiczak AF, Erbel R, Erdmann J, Eriksson JG, Farrall M, Felix SB, Ferrannini E, Ferrieres J, Ford I, Forouhi NG, Forrester T, Franco OH, Gansevoort RT, Gejman PV, Gieger C, Gottesman O, Gudnason V, Gyllensten U, Hall AS, Harris TB, Hattersley AT, Hicks AA, Hindorff LA, Hingorani AD, Hofman A, Homuth G, Hovingh GK, Humphries SE, Hunt SC, Hypponen E, Illig T, Jacobs KB, Jarvelin MR, Jockel KH, Johansen B, Jousilahti P, Jukema JW, Jula AM, Kaprio J, Kastelein JJP, Keinanen-Kiukaanniemi SM, Kiemeney LA, Knekt P, Kooner JS, Kooperberg C, Kovacs P, Kraja AT, Kumari M, Kuusisto J, Lakka TA, Langenberg C, Marchand LL, Lehtimaki T, Lyssenko V, Mannisto S, Marette A, Matise TC, McKenzie CA, McKnight B, Moll FL, Morris AD, Morris AP, Murray JC, Nelis M, Ohlsson C, Oldehinkel AJ, Ong KK, Madden PAF, Pasterkamp G, Peden JF, Peters A, Postma DS, Pramstaller PP, Price JF, Qi L, Raitakari OT, Rankinen T, Rao DC, Rice TK, Ridker PM, Rioux JD, Ritchie MD, Rudan I, Salomaa V, Samani NJ, Saramies J, Sarzynski MA, Schunkert H, Schwarz PEH, Sever P, Shuldiner AR, Sinisalo J, Stolk RP, Strauch K, Tonjes A, Tregouet DA, Tremblay A, Tremoli E, Virtamo J, Vohl MC, Volker U, Waeber G, Willemsen G, Witteman JC, Zillikens MC, Adair LS, Amouyel P, Asselbergs FW, Assimes TL, Bochud M, Boehm BO, Boerwinkle E, Bornstein SR, Bottinger EP, Bouchard C, Cauchi S, Chambers JC, Chanock SJ, Cooper RS, de Bakker PIW, Dedoussis G, Ferrucci L, Franks PW, Froguel P, Groop LC, Haiman CA, Hamsten A, Hui J, Hunter DJ, Hveem K, Kaplan RC, Kivimaki M, Kuh D, Laakso M, Liu Y, Martin NG, Marz W, Melbye M, Metspalu A, Moebus S, Munroe PB, Njolstad I, Oostra BA, Palmer CNA, Pedersen NL, Perola M, Perusse L, Peters U, Power C, Quertermous T, Rauramaa R, Rivadeneira F, Saaristo TE, Saleheen D, Sattar N, Schadt EE, Schlessinger D, Slagboom PE, Snieder H, Spector TD, Thorsteinsdottir U, Stumvoll M, Tuomilehto J, Uitterlinden AG, Uusitupa M, van der Harst P, Walker M, Wallaschofski H, Wareham NJ, Watkins H, Weir DR, Wichmann HE, Wilson JF, Zanen P, Borecki IB, Deloukas P, Fox CS, Heid IM, O'Connell JR, Strachan DP, Stefansson K, van Duijn CM, Abecasis GR, Franke L, Frayling TM, McCarthy MI, Visscher PM, Scherag A, Willer CJ, Boehnke M, Mohlke KL, Lindgren CM, Beckmann JS, Barroso I, North KE, Ingelsson E, Hirschhorn JN, Loos RJF, Speliotes EK. 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Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Troubles nutritionnels
- Attributs de la maladie
- Suralimentation
- Poids
- En surpoids
- Sensibilité aux maladies
- Prédisposition génétique à la maladie
- Conditions pathologiques, signes et symptômes
- Maladies nutritionnelles et métaboliques
- Signes et symptômes
- Score de risque génétique
- Obésité
- Acides aminés, peptides et protéines
- Protéines
- Récepteur du peptide-1 de type glucagon
- Récepteurs peptidiques de type glucagon
- Récepteurs, G-protéines G
- Récepteurs, surface cellulaire
- Protéines membranaires
- Récepteurs, hormones gastro-intestinales
- Récepteurs, peptide
- Tirzépatide
- sémaglutide
Autres numéros d'identification d'étude
- 5002
Plan pour les données individuelles des participants (IPD)
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Description du régime IPD
Informations sur les médicaments et les dispositifs, documents d'étude
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