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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Maria P Yavropoulou, MD, MSc, PDH
- 電話番号：+306936159517
- メール：myavropoulou@med.uoa.gr
研究連絡先のバックアップ
- 名前：Maria Evangelia Koloutsou, MD
- 電話番号：+306986606272
- メール：mkoloutsou@med.uoa.gr
研究場所
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Athens、ギリシャ、11527
- 募集
- Laiko General Hospital, Athens
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コンタクト：
- Maria Evangelia Koloutsou, MD
- 電話番号：+306986606272
- メール：mkoloutsou@med.uoa.gr
-
コンタクト：
- Maria Yavropoulou, MD, MSc, PHD
- 電話番号：+306936159517
- メール：myavropoulou@med.uoa.gr
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主任研究者：
- Nikolaos Tentolouris, Prof
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副調査官：
- Maria Evangelia Koloutsou, MD
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Percentage weight loss at 6 months
時間枠：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.
|
6 months
|
協力者と研究者
出版物と役立つリンク
一般刊行物
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研究記録日
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研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
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QC基準を満たした最後の更新が送信されました
最終確認日
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その他の研究ID番号
- 5002
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