Abstract:
Weight loss, whether achieved through caloric restriction or pharmacological therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is effective in reducing obesity and improving cardiometabolic health. However, a significant portion of this weight loss often comes at the cost of lean body mass, particularly skeletal muscle, which has important consequences for metabolic function, strength, and long-term weight maintenance. Recent clinical data suggest that up to 25–39% of total weight lost through these interventions may be attributable to lean mass. The role of targeted nutritional strategies, specifically higher protein intake and meal replacement in preventing muscle loss during caloric restriction or with GLP-1 RAs will be explored. Meal replacements enriched with high-quality protein have demonstrated efficacy in promoting fat loss while preserving muscle mass. For example, the use of a soy-yogurt-honey based meal replacement in a structured lifestyle program has shown significant improvements in weight management and metabolic health (Berg et al., 2025) An increase in both endogenous GLP-1 as well as in Biologically active peptides (BAPs) was seen with this soy-yogurt-honey meal replacement (Berg et al., 2022). Similarly, a randomized controlled trial by Rothacker (2000) found that meal replacements led to greater fat loss and better lean mass retention compared to traditional calorie-restricted diets. In another study, Frestedt et al. (2008) reported that a high-protein meal replacement containing leucine helped preserve lean body mass and improve metabolic markers in overweight adults. These findings suggest that the strategic use of protein-enriched meal replacements can be an effective tool in weight loss programs aimed at preserving muscle mass.This review synthesizes current evidence on the impact of both diet-induced and GLP-1–mediated weight loss on skeletal muscle, and discusses strategies to mitigate muscle loss—focusing on dietary protein intake, resistance training, and multimodal lifestyle interventions. A comprehensive, individualized approach that integrates nutritional and physical activity strategies is essential for preserving muscle mass and function in patients undergoing weight loss therapy.
