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Response to Semaglutide in Non-diabetic Obese Patients With Varying Degrees of Insulin Resistance (TRIM-IR)

1 octobre 2026 mis à jour par: ETH Zurich

Treatment Response to Incretin Mimetics in Non-diabetic Obese Patients With and Without Insulin Resistance (TRIM-IR)

Incretin mimetics are widely used pharmacological treatments for weight loss, known for their high efficacy and favorable safety profile. As the most commonly prescribed drug in this class, semaglutide is effective in both diabetic and non-diabetic individuals. However, treatment responses vary significantly, with non-diabetic individuals typically experiencing better weight loss outcomes. Despite this, up to 10% of non-diabetic individuals show little or no response to treatment, and the reasons for this variability remain unclear.

The TRIM-IR study aims to investigate the role of insulin resistance (IR) in weight loss outcomes among non-diabetic obese individuals receiving semaglutide. This single-center, observational study will assess the impact of IR on weight loss, body composition, and adipose tissue function during the first 16 weeks of semaglutide therapy. The study will also explore molecular markers of adipose tissue dysfunction, focusing on the transition from dysfunctional to healthy adipose tissue.

The investigators hypothesize, that individuals with lower IR will experience greater weight loss than those with higher IR, and that the glucose infusion rate (GIR) during hyperinsulinemic euglycemic clamp testing will correlate with weight loss variability. Secondary objectives include comparing changes in fat and lean mass, reductions in visceral fat, and improvements in adipose tissue function before and after 16 weeks of treatment. Exploratory analyses will assess adipocyte subpopulations and their response to insulin sensitivity changes.

A total of 40 participants, equally distributed by gender, will be enrolled to ensure statistical power for detecting clinically relevant differences. The study aims to optimize semaglutide use for personalized obesity treatment and provide insights into the relationship between obesity, insulin resistance, and adipose tissue plasticity, with implications for improving obesity management and cardiovascular health outcomes.

Aperçu de l'étude

Statut

Complété

Les conditions

Type d'étude

Observationnel

Inscription (Réel)

40

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Suisse
    • Canton of Aargau
      • Aarau, Canton of Aargau, Suisse, 5001
        • Cantonal Hospital Aarau

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 60 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

Méthode d'échantillonnage

Échantillon non probabiliste

Population étudiée

The investigators plan to include a total of 40 non-diabetic, obese individuals that will undergo treatment with semaglutide as a weight-loss intervention independent of our observational study. To avoid a highly heterogeneous participant group, inclusion in the study will be limited to individuals with a BMI between 30 and 40 kg/m². Patients with a prediabetic state will not be excluded.

La description

Inclusion Criteria:

  1. Age between 18 and 60 years

  2. BMI 30 - 40 kg/m2

    a. Participants must meet the eligibility criteria for coverage under the KVG (Federal Health Insurance Act) and the Specialties List, which include a weight-related comorbidity (arterial hypertension, dyslipidemia) for participants with a BMI of 30- 35 kg/m2

  3. Planned therapy with semaglutide as a weight loss intervention

  4. No known presence of a diabetic state

  5. Ability to understand and sign a Patient Information and Consent Form

Exclusion Criteria:

  1. Pregnancy or active breast feeding

    1. Therapy with semaglutide is not approved for use during pregnancy or while breastfeeding, as its safety and efficacy in these conditions have not been established.
    2. Pregnancy is an exclusion criterion for the planned investigations to avoid placing pregnant individuals under unnecessary physical or psychological stress that could pose risks to both the individual and the fetus.

  2. Medication and/or pathologies that prevent the safe execution of the fat tissue biopsies (e.g. allergy towards local anesthetics, disorders of coagulation, treatment with anticoagulants)

  3. Medical conditions that prevent examinations and testing (e.g. epilepsia, symptomatic cardiovascular disease)

  4. History of or planned bariatric surgery

  5. HbA1c ≥ 6.5% as measured by the central laboratory at screening

  6. Fasting plasma-glucose >7.0 mmol/l

  7. History of type 1 or type 2 diabetes mellitus

  8. Treatment with glucose-lowering agent(s) (e.g. Metformin) within 90 days before screening

  9. Treatment with a GLP-1 (glucagon like peptide 1) receptor agonist within 180 days before screening

  10. A self-reported change in body weight >5% within 90 days before screening

  11. Active malignancy (<2a since remission)

  12. Treatment with any medication for the indication of obesity within the past 90 days before screening

  13. Uncontrolled thyroid disease, defined as thyroid stimulating hormone (TSH) > 10 mIU/L or < 0.4 mIU/L as measured by the central laboratory at screening

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Modèles d'observation: CASE_ONLY
  • Perspectives temporelles: PROSPECTIVE

Cohortes et interventions

Groupe / Cohorte
Non-diabetic obese individuals on semaglutide for weight loss

Non-diabetic obese individuals with planned semaglutide treatment as a weight loss intervention

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Changement de poids corporel (%)
Délai: 16 semaines
16 semaines

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Change in fat mass (%)
Délai: 16 weeks

measured by DEXA (dual energy x-ray absorptiometry)
16 weeks
Change in lean mass (%)
Délai: 16 weeks

measured by DEXA
16 weeks
Change in abdominal visceral fat area (in cm2)
Délai: 16 weeks

measured by DEXA
16 weeks

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Change in cell size of adipose tissue after 16 weeks of semaglutide treatment
Délai: 16 weeks

The size of adipocytes is a direct measure of adipose tissue quality and function. It will be evaluated through histological examinations.
16 weeks
Changes in cell distribution of adipose tissue after 16 weeks of semaglutide treatment
Délai: 16 weeks

Changes in the distribution of adipocytes and other components of adipose tissue (e.g. macrophages, progenitors) serve as a direct measure of adipose tissue quality and function. It will be evaluated through histological examinations.
16 weeks
Changes in signs of fibrosis in adipose tissue after 16 weeks of semaglutide treatment
Délai: 16 weeks

Signs of fibrosis are a direct measure of adipose tissue quality and function. They will be evaluated through histopathological analysis.
16 weeks
Changes in inflammatory activity of adipose tissue after 16 weeks of semaglutide treatment
Délai: 16 weeks

Inflammatory activity, measured by the number and type of white blood cells infiltrating adipose tissue, is a direct way to assess adipose tissue quality and function. It will be evaluated by quantifying inflammatory cells within the tissue.
16 weeks
Change in adipokine secretion pattern after 16 weeks of semaglutide treatment
Délai: 16 weeks

The adipokine-secretion pattern is an indirect way to assess adipose tissue quality and function. We will analyze leptin, adipokines, and other relevant markers in blood samples and potentially in adipose tissue from strong or weak responders to identify patterns that may help predict significant changes or the absence of response.
16 weeks
Change in systemic inflammation after 16 weeks of semaglutide treatment
Délai: 16 weeks

Adipose tissue dysfunction can contribute to systemic inflammation, making it an indirect measure of adipose tissue quality. Serum levels of systemic inflammatory markers such as C-reactive protein (CRP), interleukins, and tumor necrosis factor-alpha (TNF-α) will be assessed before and after 16 weeks of semaglutide treatment.
16 weeks

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

ETH Zurich

Les enquêteurs

  • Chaise d'étude: Christian Wolfrum, Prof. Dr., ETH Zurich

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

15 mars 2025

Achèvement primaire (Réel)

6 septembre 2026

Achèvement de l'étude (Réel)

6 septembre 2026

Dates d'inscription aux études

Première soumission

18 février 2025

Première soumission répondant aux critères de contrôle qualité

26 février 2025

Première publication (Réel)

4 mars 2025

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

2 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

1 octobre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 2024-02395

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

INDÉCIS

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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