Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

Protein supplementation versus incretin-based therapies: Implications for muscle and fat mass during exercise-supported weight loss

Articles in Press

Document Type : Review Articles

Authors

Fatemeh Bagherpour 1
Hamid Arazi 2

1 Department of Exercise Physiology, Faculty of Sport Sciences, University of Guilan, Rasht, Iran

2 Department of Exercise Physiology, Faculty of Sport Sciences, Ferdowsi University of Mashhad, Mashhad, Iran

10.22122/jeoct.2026.582059.1204
Abstract
Incretin–based therapies promote weight loss primarily through appetite suppression, delayed gastric emptying, and improvements in glycemic regulation, resulting in rapid and clinically meaningful reductions in body mass. In contrast, protein-focused interventions support fat loss through enhanced satiety, preservation of diet-induced thermogenesis, and direct stimulation of muscle protein synthesis, typically producing slower but more metabolically stable changes in body composition. For physically active individuals, the interaction between these strategies and exercise introduces additional physiological considerations beyond total weight loss. Exercise, particularly resistance training, increases the demand for adequate substrate availability to support skeletal muscle maintenance, remodeling, and functional adaptation. Within this context, incretin–based therapies, induced reductions in energy intake may challenge lean mass preservation if not carefully managed, whereas protein-based strategies may align more naturally with the anabolic and recovery requirements of training. Importantly, these approaches also differ in the temporal pattern of fat loss, the extent to which lean mass is affected, and the durability of weight loss once active intervention slows or ceases, factors that are especially relevant for individuals pursuing long-term exercise adherence and performance. This review synthesizes current evidence on incretin–based therapies and protein-based dietary strategies through an exercise-relevant lens, focusing on three underexamined determinants: skeletal muscle preservation, pace of fat loss, and weight-loss maintenance. Rather than positioning these approaches as competing or hierarchical, the review aims to clarify what physiological trajectories individuals may encounter when integrating each strategy with exercise. Understanding these trajectories may help practitioners and physically active individuals make more informed, context-specific decisions when selecting fat-loss interventions.

What is already known on this subject?

• GLP-1 receptor agonists and newer incretin-based pharmacotherapies produce substantial weight loss and improve cardiometabolic health in individuals with obesity and type 2 diabetes.

• Protein-rich dietary strategies are also associated with reductions in body fat and improvements in satiety, energy expenditure, and metabolic regulation.

• Exercise, particularly resistance training, is recognized as a key intervention for preserving SMM and functional capacity during weight loss.

• Concerns have emerged regarding LBM reduction during pharmacologically induced weight loss, especially with rapid reductions in body weight.

• Long-term maintenance of weight loss remains a major challenge regardless of the intervention strategy used.

 

What this study adds?

• Provides an exercise-oriented comparison between protein supplementation strategies and incretin–based weight-loss therapies rather than evaluating either approach in isolation.

• Introduces a physiology- and practice-based framework centered on three underexplored determinants of weight-loss quality: muscle mass preservation, pace of fat loss, and long-term weight maintenance.

• Synthesizes evidence from nutritional, pharmacological, and exercise science literature to evaluate how different weight-loss strategies influence body composition beyond total weight reduction.

• Highlights the importance of considering the composition, trajectory, and sustainability of weight loss when evaluating interventions in physically active individuals.

• By integrating mechanistic, nutritional, pharmacological, and exercise-related evidence, this review provides a comprehensive framework for assessing weight-loss strategies in exercise-relevant settings.

Keywords

Incretin-based therapies
Protein diets
Muscle Health
Fat loss strategies
Subjects

Acknowledgements

None.

Funding

None.

Data availability

Review article.

Compliance with ethical standards

Conflict of interest The authors declare that there is no conflict of interest in the present research.

Ethical approval Not applicable.

Informed consent Performed. 

Informed Publication Performed. 

Author contributions 

Conceptualization: F.B., H.A, Methodology: F.B., H.A., Software: F.B., H.A., Validation: F.B., H.A.,; Formal analysis: F.B., H.A.,; Investigation: F.B., H.A.,; Resources: F.B., H.A.,; Data curation: F.B., H.A.,; Writing - original draft: F.B., H.A.,; Writing–review & editing F.B., H.A.,; Visualization: F.B., H.A.,; Supervision: H.A.; Project administration: F.B., H.A.; Funding acquisition: H.A.        

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Journal of Exercise & Organ Cross Talk

Articles in Press, Accepted Manuscript
Available Online from 01 September 2026

  • Receive Date 17 April 2026
  • Revise Date 19 June 2026
  • Accept Date 28 June 2026

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