Saving muscle while losing weight: A vital strategy for sustainable results while on glucagon-like peptide-1 related drugs

Sep 22, 2025World journal of diabetes

Keeping muscle during weight loss for lasting results with glucagon-like peptide-1 drugs

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Abstract

Over 1 billion people worldwide are affected by obesity, linked to over 230 health complications.

Weight loss of 5%-10% is clinically significant for health improvement.
Pharmacotherapy options include GLP-1 receptor agonists and their combinations, which can lead to fat mass loss.
These treatments may also cause loss of lean mass, including muscle, potentially affecting long-term weight maintenance.
More than 600 myokines related to muscle contraction have been identified, suggesting their importance in preserving muscle mass and function.
A focus on reducing fat mass while minimizing muscle loss is essential in developing new anti-obesity treatments.

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Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications, with cardiovascular disease being a leading cause of mortality. Losing 5%-10% of body weight is considered clinically significant for improving health. This weight loss can be achieved through pharmacotherapy, including glucagon-like peptide 1 (GLP-1) receptor agonists, GLP-1/glucose-dependent insulinotropic peptide dual receptor agonists, and GLP-1/glucose-dependent insulinotropic peptide/glucagon triple receptor agonists (such as semaglutide, tirzepatide, and retatrutide, respectively). While much of the weight loss comes from fat mass, these treatments also result in the loss of lean mass, including muscle. This loss of muscle may contribute to difficulties in maintaining weight over the long term and can lead to sarcopenia. Therefore, the focus of new anti-obesity treatments should be primarily on reducing fat mass while minimizing the loss of muscle mass, ideally promoting muscle gain. Research focusing on human myocytes has identified more than 600 myokines associated with muscle contraction, which may play a crucial role in preserving both muscle mass and function. We explored the potential of new anti-obesity agents and their combinations with incretin-based therapies to achieve these outcomes. Further studies are needed to better understand the functional implications of lean mass expansion during weight loss and weight maintenance programs.

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Saving muscle while losing weight: A vital strategy for sustainable results while on glucagon-like peptide-1 related drugs

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