TORONTO — GLP-1 receptor agonists (RAs) have transformed diabetes and obesity management, offering improvements in glycemic control and weight loss and reductions in cardiometabolic risk.

But “an emerging concern of these therapies is the unintended loss of skeletal muscle mass, which has important implications for metabolic health, physical function, and long-term outcomes,” said Jenna Gillen, PhD, assistant professor of exercise physiology at the University of Toronto, Toronto.

Gillan moderated a session mitigating muscle loss at the Diabetes Canada and Canadian Society of Endocrinology and Metabolism (CSEM) Professional Conference 2025.

In mouse studies, the pronounced weight loss due to GLP-1s “seems to be explained to a large extent by reductions in food intake, at least during the initial week or two,” David Wright, PhD, professor of kinesiology at the University of British Columbia in Vancouver, said during the session’s first presentation. “Importantly, we see exactly the same thing clinically as well.”

A 2021 study published in Diabetes, Obesity and Metabolism found that semaglutide reduced food intake in people with type 2 diabetes and affected appetite and food preference, including by shifting participants away from consumption of sweet or high-fat foods. “There seems to be an effect on both the total amount of calories that individuals are eating and the type of calories,” he said.

Each Meal an Opportunity

Daniel Moore, PhD, professor of muscle physiology at the University of Toronto, emphasized in his presentation that muscle breakdown is a natural process and is balanced out by muscle protein synthesis. Therefore, “what you eat and when you eat it matters for your muscles, especially around the importance of dietary protein,” he said.

He emphasized that each meal is an opportunity to rebuild muscle lost during fasting, also pointing out that muscle protein synthesis lasts for about 4-6 hours after a meal. Therefore, eating protein-rich meals or snacks throughout the day can help maintain muscle mass.

In addition, muscle breakdown is particularly high in the morning after sleep because of the longer fasting period. This finding makes breakfast a key opportunity to rebuild muscle with a protein-rich meal.

When it comes to muscle protein synthesis, not all amino acids used to build that protein are equal. Protein synthesis is “driven almost exclusively by the essential amino acids found in the protein food,” said Moore. “If we give people just the essential amino acids, we get a very similar [protein synthesis] response as if we gave them a complete protein.”

Animal sources of protein contain complete proteins, or all essential amino acids, so people who eat those regularly are likely to get enough essential amino acids. In contrast, some foods in plant-based diets may be deficient in certain amino acids, which means combining things like “beans and rice will allow for a more complete protein mixture,” said Moore.

Other factors can affect muscle protein synthesis. For example, “the obese state…can make the muscle resistant to the food that we eat,” said Moore. “We have to correct for that, which will occur through weight loss.”

Similarly, “as we age, we get less responsive to the food that we eat,” he said, older adults “need more protein in the meal” to get to the same protein saturation point as young individuals.

Regular Physical Activity

In addition to consuming sufficient complete protein, “physical activity has to be considered when talking about efficiency of food intake,” said Moore. “In my view, the only way to minimize this loss of muscle mass that we get with diet or incretin-based therapies is to be active.”

Moore said that walking 8000 steps per day is a good low-impact activity. As for resistance exercise, it doesn’t need to involve working at your maximum effort. Using lighter weights and doing 20-25 repetitions can be just as effective for preserving muscle mass as seven or eight repetitions of heavier weights, which could predispose an individual to muscle injury, he said.

Peminda K. Cabandugama, MD, DABOM, an endocrinologist, internal medicine specialist, and obesity medicine specialist at the Cleveland Clinic and spokesperson for the Obesity Society, commented on these topics for Medscape News Canada.

Muscle loss is always a concern when it comes to weight loss, whether it is driven by diet or GLP-1s, he said. Muscle loss is a particular concern for older patients, who may be prone to sarcopenic obesity (ie, the simultaneous presence of sarcopenia and excess body fat).

To mitigate the effects of muscle loss, Cabandugama recommends aiming for at least 35 g of protein per meal or around 0.4 g of protein per kg of body mass. Older adults may require more.

Regarding exercise, people should meet the US physical activity guidelines of at least 150 minutes per week of moderate-intensity physical activity and at least 2 days per week of strength training, he said. “Diet and exercise continue to be the foundation that the long-term success of weight management stands on,” said Cabandugama.

Wright, Moore, and Cabandugama reported having no relevant financial relationships.

Shawn Radcliffe is a freelance health and science journalist based in Ontario, Canada, with more than 15 years writing about general health, medical research, mental health, and other topics for print and online publications. He previously performed laboratory and clinical research and research administration at universities in Philadelphia and Portland, Oregon. He has a master’s degree in science education from Drexel University.