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

Inclusion criteria

• 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

Exclusion criteria

• 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.
• 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