The Hidden Cost of GLP-1 Weight Loss: What Happens to Muscle

By Shannon Kasun, Neuroscience Specialist

Glucagon-like peptide-1 (GLP-1) medications have surged in popularity in recent years, driven by their effectiveness for weight loss and metabolic health. Originally developed to treat type 2 diabetes, GLP-1 receptor agonists are now widely prescribed for obesity and cardiometabolic risk reduction.

GLP-1 is a naturally occurring hormone released by the gut in response to food intake. It plays a key role in blood-sugar regulation by stimulating insulin secretion, suppressing glucagon release, slowing gastric emptying, and increasing feelings of satiety. Together, these effects help regulate appetite and stabilize post-meal glucose levels.

GLP-1 receptor agonists mimic these physiological actions—reducing appetite and delaying gastric emptying to prolong satiety signals. The result is a substantial reduction in caloric intake and, for many individuals, dramatic weight loss.

While these medications are undeniably effective, an often-overlooked consequence of GLP-1–induced weight loss is its effect on skeletal muscle mass.

Weight loss is rarely composed of fat loss alone. When energy intake drops significantly—especially in the absence of resistance training and adequate protein—both fat mass and lean mass are lost. Emerging evidence suggests this effect may be particularly pronounced with GLP-1–based therapies.

Recent analyses indicate that approximately 25–39% of total weight lost during GLP-1 therapy may come from fat-free mass, including skeletal muscle (Prado et al., 2024). 

Muscle loss has real physiological consequences. Muscle—often referred to as the “currency of longevity”—is a primary driver of metabolic health, insulin sensitivity, glucose disposal, resting energy expenditure, and physical resilience across the lifespan. Excessive loss of lean mass may increase the risk of:

• Sarcopenia and frailty

• Falls, fall-related injuries, and hospitalizations

• Reductions in metabolic rate

• Declines in strength, mobility, functional capacity, and independence

  
  

Without intentional countermeasures, the body adapts to energy restriction by down-regulating metabolically expensive tissue—muscle.

The takeaway is not that GLP-1 medications should be avoided—but that they should be used strategically. Preserving lean mass requires:

• Adequate protein intake

• Progressive resistance training

• Monitoring body composition, not just scale weight

  
  

Weight loss that significantly compromises muscle may ultimately undermine long-term health and physical independence—risks that become increasingly significant with age.

For individuals using GLP-1 medications, protecting lean mass should be a priority. One of the most effective strategies is adequate protein intake. Optimal intake may be up to ~1 gram of protein per pound of lean body mass per day, with at least 25-30 grams per meal.

Equally important is regular resistance training. Incorporating 2–3 strength-training sessions per week, with movements that target major muscle groups, provides the exercise necessary to preserve muscle.

Together, sufficient protein intake and consistent strength training form a powerful counterbalance to GLP-1–induced muscle loss—helping ensure that reductions on the scale reflect fat loss, not muscle and functional capacity.

References

Prado, Carla et al. “Muscle matters: the effects of medically induced weight loss on skeletal muscle.” The lancet. Diabetes & endocrinology vol. 12,11 (2024): 785-787. doi:10.1016/S2213-8587(24)00272-9