Preserving Lean Body Mass During Weight Loss In Elderly Obese Patients With GLP-1 Receptor Agonist Treatment

This will be a single center, prospective, open label, randomized and controlled pilot study to investigate the effects of semaglutide addition to a standard weight loss intervention program for 16 weeks on body weight and composition, adipose tissue metabolism and muscle strength compared to the standard weight loss program alone in elderly obese patients.

Eligible and qualified patients will be randomized 1:1 in pairs (8 pairs) matched by age and BMI within 5% and by gender to one of two open-label interventions. Priority of enrollment will be to match already existing and non-matched pair(s) before starting new ones. However, participants will not need to wait until they are matched to be enrolled in the study. The two open-label interventions are:

1. Control group: Standard of care weight loss program that includes lifestyle changes and personalized exercise and dietary education.
2. Semaglutide group: semaglutide (up to 1mg) once weekly injection added to the standard of care weight loss program. Semaglutide dose will be started at 0.25 mg dose during the baseline visit and doubled every 2 weeks up to 1mg dose or up to maximum tolerable dose. Patients will be instructed on how to inject themselves with the drug and how to increase the dose. During dose escalation, we will be monitoring the subject more extensively (4 weeks and 8 weeks), compared to clinical practice, for any side effects including if they experience any GI side effects, and subjects will be kept at the maximum tolerable dose up to 1mg/week.

At the baseline visit, and for all other visits, patients will come fasting (10 -12 hours) to the research center. Patients will visit the research center at 4 weeks (safety visit), 8 weeks and at 16 weeks (final study assessment visit). Blood (about 25 ml), body weight and other vitals, adverse events including hypoglycemia (blood sugar <70 mg/dl) will be collected at all visits. Fat biopsy aspiration, DEXA scans, muscle strength measurement and age-appropriate quality of life questionnaire (Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) will be performed at 0- and 16-weeks visits.

All patients will receive instructions at the beginning of the study on weight loss nutritional program and appropriate physical activity to be performed for the next 16 weeks. The program will be based, in-part, on dietary and exercise habits collected at screening visit. For the entire duration of the study, participants will maintain a daily diary to document food and exercise activities to ensure compliance with lifestyle program provided. At the 4- and 8-weeks visits, the daily diary will be reviewed for food and exercise activities, and instructions will be provided again to reinforce intervention.