Effects of liraglutide treatment for 18 days on metabolic parameters, regional body composition and the myostatin-activin-follistatin-IGF-1 axis: Results from an exploratory, randomized, placebo-controlled, crossover study.

AIMS: Glucagon-like peptide-1 receptor agonists treat type 2 diabetes mellitus (T2DM), obesity and related comorbidities. Generic liraglutide recently became available, increasing its accessibility. While effective for weight and glycaemic control, its impact (magnitude, timing and regional patterns) on body composition remains uncertain. This exploratory study investigated short-term effects of liraglutide on metabolic parameters, detailed body composition, and myostatin-activin-follistatin-IGF-1 (MAFI) axis components in individuals with T2DM. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, crossover trial, 20 adults with T2DM received liraglutide (up to 1.8 mg/day) or placebo for 18 days, separated by a washout period. Dual-energy X-ray absorptiometry assessed regional fat, lean, and bone compartments. Circulating C-peptide and MAFI components were measured by enzyme-linked immunosorbent assay. Outcomes were analyzed using linear mixed models with fixed effects for sequence, as well as time, treatment, and interactions. RESULTS: Liraglutide reduced total body mass (time × treatment p = 0.04) and lowered absolute and percent android fat (time × treatment p = 0.01 and 0.04), as well as trunk fat mass (time × treatment p = 0.04), with no changes in lean or bone compartments over 18 days. In the liraglutide group, C-peptide decreased while total IGF-1 modestly increased (time × treatment p = 0.026 and 0.002, respectively), with no treatment effects on other MAFI components. CONCLUSIONS: Short-term liraglutide reduced total body mass and regional trunk and android fat while also improving glycaemia, with no measurable effects on lean or bone tissue. Selective effects on hormones were observed, though their biological plausibility and clinical relevance as compensatory changes maintaining nonfat mass require further investigation. These findings provide early insights into initial responses to liraglutide therapy. Longer studies should assess whether sustained treatment modifies total and lean mass as well as endocrine regulators of muscle preservation.