Weight Loss Medication Side Effects: Muscle-Related Risks Identified in New Study - The Nutrition Insider (2024)

The use of GLP-1 receptor agonists (AKA semaglutide, Ozempic, and Wegovy) has exploded in recent years for weight loss or type 2 diabetes management.

But while these medications can be lifesaving for some, they also have some serious potential side effects that are now being recognized—and muscle loss is one of them.

In a new article in the November 2024 issue of The Lancet Diabetes & Endocrinology, researchers highlight the importance of maintaining muscle mass when taking GLP-1 agonists for medically induced weight loss.¹

Weight Loss Medication Side Effects: Muscle Loss

According to this paper, muscle loss (a decrease in fat-free mass) can account for 25 to 39% of the total weight loss when on Ozempic or similar drugs, which can lead to significant adverse health effects.

When you lose weight quickly—as these medications promote—you don’t just lose fat; you also lose muscle. This is because your body needs to break down muscle tissue for energy, especially if you don’t eat enough protein—which most people on GLP-1 agonists don’t due to appetite suppression.

The rates of muscle decline seen with weight loss medications like Ozempic are significantly higher than those seen with normal aging or non-pharmaceutical weight loss programs, which can lead to sarcopenia.

Sarcopenia, or the loss of muscle mass, strength, and performance, typically only occurs with advancing age or immobility, but people can see significant muscle loss much earlier—especially when losing weight quickly.

Most people lose muscle mass by approximately 3 to 8% per decade after age 30, with declines increasing much more after age 60.²

It’s well-known that having enough skeletal muscle is vital for remaining strong and mobile. Still, many may not know its importance for other health outcomes—including bone density, immune function, cardiovascular health, blood sugar regulation, and even longevity.³

Muscle mass is also considered a metabolic organ, acting as a reservoir for amino acids (including those that respond to infection, trauma, and stress). It also significantly impacts blood sugar regulation by promoting glucose uptake into the muscles. Essentially, muscle tissue acts like a “sponge” for sugar—the more muscle you have, the better able you are to regulate blood sugar.

Our muscle cells also produce signaling molecules called myokines, which help to modulate metabolism, inflammation, immunity, and energy balance. The association between muscle mass and immunity is particularly interesting, as they have a bidirectional relationship—meaning that low muscle mass is linked to poor immunity and vice versa.

More muscle mass also means a higher resting metabolic rate, or how many calories you burn at rest. When you lose muscle, your resting metabolic rate decreases, meaning that you need to consume fewer calories to maintain the new lower weight.

Often known as the “Biggest Loser Effect,” this is one reason why people tend not to be able to maintain extreme weight loss. In the case of GLP-1 agonists, many people who lose weight gain it back (now known as “Ozempic Rebound”)—but they tend to gain back fat, not the lost muscle.⁴

Women taking GLP-1 agonists may need to pay particularly close attention to their muscle maintenance, as women are already more likely to have lower muscle mass than men.⁵ Women of all ages need to prioritize their muscle stores, as muscle is vital for preventing osteoporosis, increasing metabolic rate, improving balance, and promoting sleep quality.⁶

Weight Loss Medications and Sarcopenic Obesity

Some people taking weight loss medications may have sarcopenic obesity—a condition where obesity coexists with sarcopenia or low muscle mass.

Sarcopenic obesity contributes significantly to adverse health outcomes, including cardiovascular disease and higher mortality rates. In these cases, it is essential to combine weight loss with practices to prevent more muscle loss, such as elevated protein intake with strength training programs.

However, as GLP-1 receptor agonists work by reducing appetite, it may be difficult for people to get adequate protein (and other nutrients) to prevent this loss. Ongoing clinical trials are looking at other drugs to mitigate muscle loss, which could help with this issue—but depending on any potential side effects of the new drugs, they could also introduce new problems.

If you’re concerned about sarcopenia and you don’t have any underlying kidney issues, you could take creatine, a safe and effective supplement that is well-known for preventing muscle protein breakdown which could potentially slow down sarcopenia. Always speak with your doctor before adding supplements to your regimen.

Overall, GLP-1 receptor agonist medications can be incredibly useful for some people with obesity, but methods to maintain or increase muscle mass are imperative, as the benefits of losing weight may not outweigh (no pun intended) the risks of sarcopenia.