Response to Semaglutide in Non-diabetic Obese Patients With Varying Degrees of Insulin Resistance

NCT06856291 | Recruiting

• 1 other identifier: 2024-02395
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity and Obesity-related Medical Conditions; Obesity and Overweight; Insulin Sensitivity/Resistance; Semaglutide

Keywords

Insulin Resistance; incretin mimetics; semaglutide; weight loss; adipose tissue function; obesity; hyperinsulinemic euglycemic clamp; obesity management; insulin sensitivity

Outcome Measures

Primary Outcomes (1)

• Change in body weight (%)

  16 weeks

Secondary Outcomes (3)

• Change in fat mass (%)

  16 weeks

• Change in lean mass (%)

  16 weeks

• Change in abdominal visceral fat area (in cm2)

  16 weeks

Other Outcomes (6)

• Change in cell size of adipose tissue after 16 weeks of semaglutide treatment

  16 weeks

• Changes in cell distribution of adipose tissue after 16 weeks of semaglutide treatment

  16 weeks

• Changes in signs of fibrosis in adipose tissue after 16 weeks of semaglutide treatment

  16 weeks

Study Arms (1)

Non-diabetic obese individuals on semaglutide for weight loss

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

Eligibility Criteria

• Age: 18 Years - 60 Years
• Gender Eligibility Details: Planned gender distribution of females:males is 1:1, determined by biological sex
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Age between 18 and 60 years
• 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
• Planned therapy with semaglutide as a weight loss intervention
• No known presence of a diabetic state
• Ability to understand and sign a Patient Information and Consent Form

You may not qualify if:

• 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.
• 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)
• Medical conditions that prevent examinations and testing (e.g. epilepsia, symptomatic cardiovascular disease)
• History of or planned bariatric surgery
• HbA1c ≥ 6.5% as measured by the central laboratory at screening
• Fasting plasma-glucose \>7.0 mmol/l
• History of type 1 or type 2 diabetes mellitus
• Treatment with glucose-lowering agent(s) (e.g. Metformin) within 90 days before screening
• Treatment with a GLP-1 (glucagon like peptide 1) receptor agonist within 180 days before screening
• A self-reported change in body weight \>5% within 90 days before screening
• Active malignancy (\<2a since remission)
• Treatment with any medication for the indication of obesity within the past 90 days before screening
• 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

Sponsors & Collaborators

• ETH Zurich: lead

Study Sites (1)

Cantonal Hospital Aarau

Aarau, Canton of Aargau, 5001, Switzerland

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood analyses (EDTA, Hep, glucose measurement throughout clamp test) Adipose tissue biopsies

MeSH Terms

Conditions

Obesity; Overweight; Insulin Resistance; Weight Loss

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Body Weight Changes

Study Officials

• Christian Wolfrum, Prof. Dr.

  ETH Zurich

  STUDY CHAIR

Central Study Contacts

Katja M Leitner, Dr. med. univ.

CONTACT

+41628384184; katja.leitner@hest.ethz.ch

Slavica Akunna, Study Nurse

CONTACT

+41628384999; slavica.akunna@ksa.ch

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: March 4, 2025
• Study Start: March 15, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: March 25, 2025

Record last verified: 2025-02

Locations

CH (1)