Semaglutide for the treatment of visceral obesity in people with HIV with body mass index <30 kg/m2 and without diabetes: a randomized clinical trial to explore immune metabolism, systemic and vascular inflammation assessed with Positron Emission Tomography

Lab values

• Known diabetes mellitus • Previous use of semaglutide or other GLP-1 receptor agonists • Previous major cardiovascular event (myocardial infarction, stroke, coronary or peripheral revascularization) • Clinically relevant active malignancy, except radically treated non-melanoma skin cancer • Severe hepatic or renal impairment as judged by the investigator • Personal or family history of medullary thyroid cancer • Pregnancy or breastfeeding • Contraindication to PET or semaglutide • Any active or chronic uncontrolled inflammatory condition, infection or cancer • Any clinically relevant illness within 14 days prior to study entry not explicitly excluded by the protocol • A physical or psychiatric disability, or a laboratory abnormality, that might place the subject at increased risk by being exposed to the medications in this study or which might confound the interpretation of this investigation • Regular use of immunomodulators or agents which could impact inflammation (regular use of NSAIDs is allowed if constant and uninterrupted for 6 months, with no plans to alter it) • Use of megestrol acetate, testosterone, or any steroid use beyond normal amounts found in the body within 6 months of study entry, or intention to start • Elevated serum lipase level >1.5 × the upper limit of normal at screening • History of excessive alcohol use (on average 2 or more drinks a day) • History of pancreatitis • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC

• Age >18 years • HIV infection on stable ART for at least 12 weeks • Undetectable HIV RNA (<50 copies/mL) • BMI ≥25 and <30 kg/m2 • DEXA-derived VAT area ≥140 cm2 (study-specific operational threshold) • Waist circumference of at least 94 cm in men or at least 80 cm in women, or waist to hip ratio of at least 1.00 in men or at least 0.85 in women • Provision of signed and dated informed consent form, and capability of reading and comprehending the informed consent • Willingness to comply with all study procedures and availability for the duration of the study • No plans to undergo any other weight-loss programme or bariatric/metabolic surgery during the study period • For women of childbearing potential (WOCBP, as defined in Appendix 1): negative pregnancy test at screening and at baseline, and willingness to use a highly effective contraceptive method (Appendix 1) throughout the study and, if randomised to semaglutide, for at least 2 months after the last dose of IMP (i.e. beyond the minimum of 7 weeks off treatment)