Ozempic and Wegovy: Scientists Examine GLP-1 Agonists and Muscle Loss

Medicines such as Ozempic and Wegovy are widely known for helping people lose weight, yet some scientists are seeking a clearer understanding of their effect on muscle loss.

In a new commentary in The Lancet, an international group of researchers says too little is known about how GLP-1 receptor agonists affect muscles.

GLP-1 receptor agonists: established benefits and unanswered questions

The authors recognise that GLP-1 agonists have "shown substantial benefits" for people worldwide. Originally approved for the treatment of type 2 diabetes, early research indicates these medicines can also help people to lose weight.

People who do not lose weight can still experience better kidney and heart health, lowering their likelihood of stroke or cardiac arrest.

Nevertheless, the scientists are concerned by early findings suggesting that GLP-1 agonists may be linked to marginally greater losses of non-fat tissue than weight loss achieved without medication.

A reduction in fat-free tissue does not necessarily provide a complete picture of muscle loss, and reduced muscle mass does not automatically mean poorer strength or mobility. However, dietician Carla Prado, biomedical researchers Stuart Phillips and Steven Heymsfield, and nutritionist Cristina Gonzalez say more evidence is needed before firm conclusions can be drawn.

"At the time of writing, there are no data to establish whether treatment with GLP-1 receptor agonists is associated with physical frailty or [a loss of muscle mass]," the team writes.

"These effects would require long-term studies, which are not yet available, and the studies conducted to date were not designed to answer these questions."

Why muscle mass matters during weight loss

Although early studies indicate that the weight loss associated with GLP-1 agonists does not affect strength, the authors point out that strength "is only one aspect of muscles' importance."

Muscles are essential not just for movement but also for metabolism, immune function, and the body's response to stress and trauma, they explain.

Muscle mass additionally enables the body to absorb glucose in response to insulin.

The researchers are concerned that muscle loss could further worsen risk factors present in some patients taking GLP-1 agonists, including metabolic dysfunction, inflammation, inadequate dietary intake and low levels of physical activity.

In light of these risks, the authors conclude that "these highly effective medications should be used strategically. This strategy can be accomplished with concurrent nutrition and exercise interventions."

Exercise and nutrition alongside GLP-1 agonists

Research has found that, following weight loss, declining skeletal muscle mass can be partly addressed through greater protein consumption or exercise. Some estimates suggest resistance training can reduce losses of fat-free mass by 50 to 95 percent.

These findings support the case for prescribing exercise programmes and nutritional guidance alongside GLP-1 agonists to achieve the best outcomes.

When people discontinue these appetite-suppressing medicines, they usually regain roughly two-thirds of the weight they lost within a year. However, participants in a recent clinical trial who took part in supervised exercise programmes were more successful at maintaining weight loss.

"Additionally," the team writes, "ongoing studies are exploring ways to prevent or mitigate muscle loss with drugs… which could offer solutions for preserving muscle mass in individuals undergoing weight loss treatments."

The possibility of muscle loss does not mean patients should stop using GLP-1 agonists. But because muscles are so important to human health, the researchers say further knowledge is needed.

The commentary was published in The Lancet: Diabetes & Endocrinology.