University of Alberta researchers raise concerns over muscle loss with popular obesity drugs

November 8, 2024 Canuck

Researchers at the University of Alberta are weighing the effects of trendy weight-loss medications like Ozempic on muscle mass.

New work is “calling attention to something called quality of weight loss,” said Carla Prado, a professor of human nutrition, and Canada Research Chair in Integrative Nutrition, body composition and energy metabolism at the U of A.

Prado and other researchers examined muscle loss, studying how rapid weight loss using drugs like semaglutide and tirzepatide — better known by the brand names Ozempic and Mounjaro — can change a patient’s physiology.

Prado and colleagues from McMaster University and the Pennington Biomedical Research Center in Louisiana, published a commentary in The Lancet this month that suggests the drugs have raised concerns about the potential for substantial muscle loss.

Muscle accounts for as much as 39 per cent of total weight loss over a period of 36 to 72 weeks, the commentary suggests.

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Ozempic is one of the most recognizable weight-loss drugs on the market. The semaglutide injection was approved by Health Canada in 2018 as a treatment for Type 2 diabetes, before the weight-loss benefits of the drug shot it to stardom.

It’s part of a group of drugs classified as GLP-1 receptor agonists —- or GLP-1 RAs— medications that can control blood sugar levels and initiate weight loss. These include tirzepatide and retatrutide, a drug not yet on the market.

Prado’s project brought together experts to look at the research gathered on GLP-1 RAs.

Weight loss at what cost?

“When people are losing weight, they will always lose muscle,” Prado told CBC. Due to the massive amount of weight patients can lose with these drugs, the muscle loss is significant.

“For example if a person would lose 22 pounds, that could be anywhere from 5.5 pounds to 8.8 pounds of muscle,” she said.

There’s also a risk of sarcopenic obesity, a combination of obesity and low skeletal muscle mass.

This can be a concern when people take temporary breaks from these medications due to a lapse in insurance coverage or negative side effects.

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Lost muscle weakens the immune system and can reduce the ability to recover from illness or injuries. It also helps regulate blood sugar and amino acids. As we age we lose muscle naturally, and earlier muscle loss could lead to challenges in later years.

“We don’t want to alarm anyone,” Prado told CBC’s Radio Active. “What we want people to understand is that even with these medications we can’t forget about nutrition and exercise.”

From humans to mice

Jason Dyck, a professor in the department of pediatrics and director of the Cardiovascular Research Centre at the University of Alberta, is also doing research on the effects of weight-loss drugs on muscle mass.

In October, Dyck and other researchers published a research paper in the Journal of the American College of Cardiology that looked at the effects of semaglutide medications in mice.

“We were struck by the amount of skeletal muscle loss that was observed in the clinical trials with people using Ozempic,” Dyck said.

In the study, obese mice were given Ozempic until they lost weight. Researchers found that the significant reduction in body weight from the drugs led to a decrease in heart muscle.

Two women stand in a doctors office, looking at a patient sitting on a bed wearing a blue gown. Behind them is a chart of the human anatomy. — Professor Carla Prado, centre, says the magnitude of muscle loss from GLP1-RA drugs is concerning. She is reviewing effects of the popular weight-loss drugs. (Submitted by Carla Prado)

Replicating the process but with lean mice, the researchers discovered the same smaller-heart condition. While it might sound alarming, Dyck cautioned that it’s not necessarily a red flag.

“We see no overt signs of cardiac injury,” he said. “It seems to be very different than a pathology that results in a small heart, at least in these early stages.”

The finding comes after recent clinical trials demonstrated the benefit these types of medications may have on certain forms of cardiovascular disease causing heart attacks, strokes and deaths.

The biggest concern, Dyck said, is those who are taking GLP-1 RAs for minor weight loss, and could be seeing potential risks without reaping the benefits these drugs have been proven to have for patients with diabetes and other health challenges associated with obesity.

“My enthusiasm for this class of drugs is quite high,” Dyck said, “but with anything we have to monitor and be aware of potential side effects.”

Prado and Dyck are now hoping to work together to research the long-term effects of these medications, to better support patients and ensure skeletal and cardiac muscle isn’t a casualty of weight loss.

“People may think, ‘Oh, well, we’ve found the solution, let’s just take this medication.’ But really that’s not the case,” Prado said.

“We need better studies, we need better regulations of the medications when it comes to the quality of the weight lost.”

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