Effect of a Food for Special Medical Purposes on Muscle Mass Preservation During GLP-1 RAs Weight Loss Treatment

This randomized, double-blind, placebo-controlled investigates whether a Food for Special Medical Purposes (FSMP) can help preserve appendicular skeletal muscle mass (ASMM) in adults undergoing weight loss treatment with GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists.

Eligible participants are adults with obesity or overweight with comorbidities who are initiating GLP-1-based therapy as part of standard clinical management. Participants are randomized in a 1:1 ratio to receive either the FSMP or a matching placebo for 24 weeks, in addition to their ongoing GLP-1 RA or dual GIP/GLP-1 RA therapy. Study visits occur at baseline, 8 weeks, 16 weeks, and 24 weeks.

This trial aims to determine whether targeted nutritional support can mitigate the loss of lean mass commonly observed during pharmacologically assisted weight loss, thereby improving functional outcomes and overall patient well-being.

Inclusion criteria

• Age ≥18 years and ≤ 65 years old;
• BMI ≥ 30 Kg/m2 and ≤45 kg/m2
• BMI from 27 kg/m2 to 30 Kg/m2 with at least one associated co-morbidity related to overweight [e.g. dysglycemia (pre-diabetes and/or metabolic syndrome), hypertension, dyslipidemia, obstructive sleep apnea syndrome (OSAS], or cardiovascular disease]
• Starting to use a GLP-1 RAs (liraglutide, semaglutide) or dual GIP and GLP-1 RAs (tirzepatide) for weight reduction; patient can be enrolled if they start the treatment at the time of enrollment or up to 2 weeks
• Diet composition adjusted to provide 0.9-1.1 g/Kg ideal body weight proteins
• Signed informed consent

Exclusion criteria

• Type I and Type II diabetes; patients with pre-diabetes and/or metabolic syndrome and assuming Metformin and SGLT-2 inhibitors can be enrolled
• Monogenic obesity (Subjects with a known diagnosis of monogenic obesity, including but not limited to pathogenic mutations in LEP, LEPR, MC4R, POMC, PCSK1, or other genes known to cause monogenic forms of early-onset or syndromic obesity)
• Reduced kidney function, defined as eGFR < 60 mL/min/1.73 m², calculated using the CKD-EPI equation (see Appendix 1)
• Oncologic patients in active treatments
• Hypersensitivity to any of the constituents of the study product
• Pregnancy
• Breastfeeding
• Use of meal replacements for a diet enriched with aminoacids and/or HMB
• Use of food supplements containing aminoacids and/or HMB; patients can be included in the study if they undergo a washout period of at least 15 days