Randomized Crossover Trial to Assess GH and Liraglutide Effects on AgRP in Healthy and GH-Deficient Adults

Growth hormone (GH) deficiency is associated with metabolic disturbances, including altered body composition and insulin sensitivity. Liraglutide, a GLP-1 receptor agonist, is widely used for type 2 diabetes and obesity due to its effects on glucose homeostasis, appetite regulation, and weight loss. Agouti-related peptide (AgRP) is a potent orexigenic neuropeptide, playing a critical role in appetite stimulation and energy balance within the hypothalamus. Understanding how GH and liraglutide, both individually and in combination, modulate AgRP and other metabolic parameters in both healthy and GH-deficient individuals could reveal novel therapeutic strategies for metabolic dysfunction.

This randomized, placebo-controlled, cross-over study will enroll healthy and GH-deficient adults aged 18-45 years. The design includes four treatment arms, each lasting 21 days, separated by 8-week washout periods. Participants will receive, in random order: i) GH alone, ii) GH with liraglutide, iii) liraglutide alone, and iv) placebo. Each phase comprises a 7-day baseline with 2 days of testing, followed by 21 days on therapy with visits on days 2, 7, 14, and 21. Primary endpoints include blood sampling (likely for AgRP levels), assessments of insulin resistance, energy expenditure, and body composition before, during, and after each arm.