Does retatrutide (generic name) cause muscle loss or only fat loss?

Retatrutide Causes Both Fat Loss and Some Muscle Loss

Retatrutide causes significant fat loss but also leads to some lean mass loss, with approximately 10% of total weight loss coming from lean tissue. 1

Body Composition Effects of Retatrutide

• Retatrutide is a triple-hormone-receptor agonist that targets glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors, resulting in substantial weight reduction 2
• In a phase 2 clinical trial, retatrutide demonstrated dose-dependent weight loss of up to 24.2% at the highest dose (12mg) after 48 weeks 2
• A substudy specifically examining body composition showed retatrutide reduced total fat mass by up to 26.1% at the 8mg dose 1
• While primarily causing fat loss, retatrutide also results in some lean mass loss, similar to other incretin-based medications 1, 3
• The proportion of lean mass loss to total weight loss with retatrutide is comparable to other obesity treatments, suggesting it doesn't cause disproportionate muscle loss 1

Muscle Loss Concerns

• Incretin-based medications including retatrutide can cause approximately 10% loss of lean mass (about 6kg), which is comparable to a decade or more of aging 3
• Maintaining muscle mass is crucial for preventing sarcopenia and frailty, which are strongly linked to morbidity and mortality 3
• The loss of muscle mass can affect physical function, as muscle power is directly proportional to its cross-sectional area 4
• Reduced fat-free mass is associated with impaired respiratory muscle strength and decreased health-related quality of life 4

Optimizing Body Composition During Treatment

• Resistance training is strongly recommended as an adjunct to retatrutide therapy to preserve lean mass while achieving fat loss 3
• Supervised resistance exercise training interventions lasting more than 10 weeks can increase lean mass by approximately 3kg and strength by about 25% in both men and women 3
• Resistance training not only helps preserve muscle mass but also contributes to the reduction of visceral adipose tissue, which is associated with metabolic syndrome 4
• Adequate protein intake is crucial for stimulating protein synthesis to maintain or restore fat-free mass during weight loss 4

Clinical Implications

• When monitoring patients on retatrutide, assessment of body composition rather than just body weight is important, as favorable improvements in body composition may go undetected in patients whose weight remains unchanged 4
• Weight loss in general is associated with improved cardiovascular risk factors, including reduced risk of type 2 diabetes and hypertension 4
• Retatrutide's effects on body composition should be considered in the context of its significant benefits for glycemic control and overall weight reduction 5
• For patients at risk of sarcopenia or with existing muscle weakness, particular attention should be paid to implementing strategies to preserve muscle mass during retatrutide treatment 3

Practical Recommendations

• Consider baseline assessment of body composition before starting retatrutide therapy to better track changes in fat and lean mass 4
• Implement a structured resistance training program concurrently with retatrutide treatment to optimize body composition changes 3
• Monitor for signs of excessive muscle loss, particularly in older adults or those with pre-existing sarcopenia 4
• Ensure adequate protein intake to support muscle preservation during weight loss 4