Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

Area of Science:

• Endocrinology
• Metabolism
• Exercise Physiology

Background:

• New antiobesity medications, including incretin-based therapies like GLP-1 receptor agonists (GLP-1RA), promote substantial weight loss.
• These medications, such as liraglutide, semaglutide, tirzepatide, and retatrutide, also improve metabolic markers but cause significant lean mass loss.
• Maintaining lean mass is vital for preventing age-related sarcopenia, frailty, and associated morbidity/mortality.

Purpose of the Study:

• To review the impact of incretin-based antiobesity medications on lean mass.
• To highlight the importance of resistance exercise in preserving muscle during pharmacotherapy.
• To propose resistance exercise as an adjunct to optimize body composition changes.

Main Methods:

• Narrative review of current literature on incretin-based weight loss medications.
• Analysis of studies investigating lean mass loss associated with these agents.
• Examination of resistance exercise interventions and their effects on lean mass and strength.

Main Results:

• Incretin-based medications cause approximately 10% lean mass loss, similar to aging.
• Resistance exercise training (>10 weeks) can increase lean mass and strength.
• Combining exercise with incretin therapy may optimize body composition and prevent weight regain.

Conclusions:

• Incretin therapy leads to significant lean mass reduction, posing risks for sarcopenia and frailty.
• Resistance exercise is a viable strategy to counteract lean mass loss during and after incretin therapy.
• Tailored resistance training should be recommended alongside incretin medications to preserve muscle and optimize fat loss.