Actively Recruiting

Age: 18Years - 60Years
All Genders
NCT06856291

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

Led by ETH Zurich · Updated on 2025-03-25

40

Participants Needed

1

Research Sites

76 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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

Official Title

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

Who Can Participate

Age: 18Years - 60Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age between 18 and 60 years
  • BMI between 30 and 40 kg/m2
  • For BMI 30-35 kg/m2, a weight-related comorbidity such as arterial hypertension or dyslipidemia is required
  • Planned therapy with semaglutide for weight loss
  • No known diabetes
  • Ability to understand and sign informed consent
Not Eligible

You will not qualify if you...

  • Pregnancy or active breastfeeding
  • Conditions or medications preventing safe fat tissue biopsies, including allergy to local anesthetics, coagulation disorders, or anticoagulant treatment
  • Medical conditions preventing examinations, such as epilepsy or symptomatic cardiovascular disease
  • History of or planned bariatric surgery
  • HbA1c 6.5% or higher
  • Fasting plasma glucose above 7.0 mmol/l
  • History of type 1 or type 2 diabetes
  • Treatment with glucose-lowering agents within 90 days before screening
  • Treatment with GLP-1 receptor agonists within 180 days before screening
  • Weight change greater than 5% within 90 days before screening
  • Active malignancy within the past 2 years
  • Treatment with obesity medications within 90 days before screening
  • Uncontrolled thyroid disease with TSH above 10 mIU/L or below 0.4 mIU/L at screening

AI-Screening

AI-Powered Screening

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Trial Site Locations

Total: 1 location

1

Cantonal Hospital Aarau

Aarau, Canton of Aargau, Switzerland, 5001

Actively Recruiting

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Research Team

K

Katja M Leitner, Dr. med. univ.

CONTACT

S

Slavica Akunna, Study Nurse

CONTACT

How is the study designed?

Study Type

OBSERVATIONAL

Masking

N/A

Allocation

N/A

Model

N/A

Primary Purpose

N/A

Number of Arms

1

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