How do GLP1s impact muscle mass?

When my patients are considering starting on GLP1s, one of the things I assess for is malnutrition risk. And I admit, I worry about about these medications for those with high nutrition risk because I worry about frailty. Want to know why frailty matters? Check out my previous post here.

So what evidence supports my worry? Today’s post is a summary of this systematic review reporting on the impacts of semaglutide (a GLP1) on lean mass.

What is lean mass?

The authors of the paper describe that lean mass is the total weight excluding fat. This includes:

• Muscles
• Bones
• Organs
• Non-fat tissues

The weight of the muscles attached to the skeleton is the skeletal muscle mass. These muscles are used for movement.

Why do we care about lean mass?

Losses in lean mass can result in:

• sarcopenia (which is a loss of both muscle mass and function)
• impacts on glucose homeostasis as muscles are important users of glucose

What did the authors do?

In this article, clinical trials investigating semaglutide and lean mass were included. 8 studies met the full inclusion criteria, summarizing the results from 1,541 adults.

What did they find?

All studies reported weight loss but the amount of lean mass loss differed between studies. In some studies lean mass loss was as low as 0%, while in others it was as 40% of the total weight loss. Studies that included fewer people and were of shorter duration were less likely to report losses (or reported smaller losses) in lean mass.

The authors state that the findings from the larger trials suggest caution may be warranted due to the potential negative impacts on lean mass observed.

What did the authors conclude?

The authors acknowledge that losing lean mass isn’t ideal, however it is likely less concerning than higher proportions of body fat. In this way, for adults living with overweight or obesity, the risk of this medication on lean mass is outweighed by the benefits. However, for adults living at a healthy body weight, the risk of lean mass loss may not outweigh the benefits.

Additionally the authors point out, that even for those with overweight and obesity, those who start this medication with low lean mass may experience increased rates of sarcopenia. In these instances, the risks may outweigh the benefits.

The authors encourage future trials to ensure they include investigations on muscle mass and function with these medications.

Take Aways

Semaglutide is associated with reductions in both adipose and lean mass when weight loss occurs. While as much as 56% of the weight loss may be coming from adipose, the other portion is coming from lean mass.

For those who already have low lean mass, use of these medications should be done with caution to prevent further losses, which can result in loss of function.