Response to Semaglutide in Non-diabetic Obese Patients With Varying Degrees of Insulin Resistance (TRIM-IR)
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.
Descripción general del estudio
Estado
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
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Canton of Aargau
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Aarau, Canton of Aargau, Suiza, 5001
- Cantonal Hospital Aarau
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
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.
Descripción
Inclusion Criteria:
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Age between 18 and 60 years
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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
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Planned therapy with semaglutide as a weight loss intervention
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No known presence of a diabetic state
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Ability to understand and sign a Patient Information and Consent Form
Exclusion Criteria:
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Pregnancy or active breast feeding
- 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.
- 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.
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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)
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Medical conditions that prevent examinations and testing (e.g. epilepsia, symptomatic cardiovascular disease)
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History of or planned bariatric surgery
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HbA1c ≥ 6.5% as measured by the central laboratory at screening
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Fasting plasma-glucose >7.0 mmol/l
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History of type 1 or type 2 diabetes mellitus
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Treatment with glucose-lowering agent(s) (e.g. Metformin) within 90 days before screening
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Treatment with a GLP-1 (glucagon like peptide 1) receptor agonist within 180 days before screening
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A self-reported change in body weight >5% within 90 days before screening
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Active malignancy (<2a since remission)
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Treatment with any medication for the indication of obesity within the past 90 days before screening
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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 de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: CASE_ONLY
- Perspectivas temporales: PROSPECTIVE
Cohortes e Intervenciones
Grupo / Cohorte |
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Non-diabetic obese individuals on semaglutide for weight loss
Non-diabetic obese individuals with planned semaglutide treatment as a weight loss intervention |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Cambio en el peso corporal (%)
Periodo de tiempo: 16 semanas
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16 semanas
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in fat mass (%)
Periodo de tiempo: 16 weeks
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measured by DEXA (dual energy x-ray absorptiometry) |
16 weeks
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Change in lean mass (%)
Periodo de tiempo: 16 weeks
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measured by DEXA |
16 weeks
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Change in abdominal visceral fat area (in cm2)
Periodo de tiempo: 16 weeks
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measured by DEXA |
16 weeks
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in cell size of adipose tissue after 16 weeks of semaglutide treatment
Periodo de tiempo: 16 weeks
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The size of adipocytes is a direct measure of adipose tissue quality and function. It will be evaluated through histological examinations. |
16 weeks
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Changes in cell distribution of adipose tissue after 16 weeks of semaglutide treatment
Periodo de tiempo: 16 weeks
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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
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Changes in signs of fibrosis in adipose tissue after 16 weeks of semaglutide treatment
Periodo de tiempo: 16 weeks
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Signs of fibrosis are a direct measure of adipose tissue quality and function. They will be evaluated through histopathological analysis. |
16 weeks
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Changes in inflammatory activity of adipose tissue after 16 weeks of semaglutide treatment
Periodo de tiempo: 16 weeks
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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
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Change in adipokine secretion pattern after 16 weeks of semaglutide treatment
Periodo de tiempo: 16 weeks
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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
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Change in systemic inflammation after 16 weeks of semaglutide treatment
Periodo de tiempo: 16 weeks
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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
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Silla de estudio: Christian Wolfrum, Prof. Dr., ETH Zurich
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Trastornos Nutricionales
- Enfermedades metabólicas
- Sobrenutrición
- Peso corporal
- Cambios en el peso corporal
- Trastornos del metabolismo de la glucosa
- Hiperinsulinismo
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades Nutricionales y Metabólicas
- Signos y síntomas
- Exceso de peso
- Obesidad
- Pérdida de peso
- Resistencia a la insulina
Otros números de identificación del estudio
- 2024-02395
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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