Preserving Lean Body Mass in Patients Taking GLP-1 for Weight Loss
Key Findings
- GLP-1 agonists like semaglutide can help patients achieve rapid weight loss, but some patients may be concerned about "losing too much weight," or the loss of fat-free mass
- In a recent Medical Grand Rounds presentation, Mass General Brigham researchers reviewed current data and discussed the clinical implications of GLP-1 and other weight loss approaches on muscle and body composition
- Weight loss paradigms universally induce the loss of lean body mass, not just GLP-1, but muscle-sparing therapies can help prevent it
- While more accurate tools for measuring body composition are needed, combining GLP-1 with both exercise and high protein diet has shown benefit in preserving bone and muscle mass
Glucagon-like peptide-1 (GLP-1) agonists such as semaglutide are increasingly being used to treat obesity and promote weight loss. Patients may be concerned about GLP-1 side effects, and some, including "super responders" who achieve rapid weight loss with the treatment, may worry about inadvertent bone or muscle loss.
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In a recent Medical Grand Rounds presentation, Mass General Brigham researchers translated the field of body composition into the current debate about the loss of lean body mass in patients taking GLP-1 for weight loss. They report that while more accurate tools are needed to measure body composition and functionality, combining exercise and high protein diet has shown benefit in preventing bone and muscle loss.
The presenters included Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women's Hospital, Armen Yerevanian, MD, an endocrinologist and internist at Massachusetts General Hospital, and Jody Dushay, MD, MMSc, an attending physician at Beth Israel Deaconess Medical Center.
Preventing GLP-1 Muscle and Bone Loss
The presenters discussed the current tools and limitations of measuring body composition, and how the loss of lean body mass is universally induced by weight loss, not just with the use of GLP-1 agonists.
"In simple terms, when you lose weight, you are decreasing caloric intake in terms of proteins, carbohydrates, and fats," says Dr. Apovian. "The brain needs glucose. Fat by itself cannot be turned into glucose, and that is the major reason why muscle loss is inevitable when you decrease caloric intake."
Eating a low carbohydrate, protein-sparing diet causes the body to develop ketosis, where ketones are produced to feed the brain. This results in increased fat loss and decreased loss of muscle mass.
"Ketosis blocks the glucose-alanine cycle, which means it blocks the extrusion of branch chain amino acids coming from muscle. So it protects your muscle mass, and ketones feed the brain, so you don't need to produce glucose from muscle," Dr. Apovian explains.
They report that current data shows combining a high protein diet and consistent exercise with GLP-1 treatment has the greatest benefit in preserving bone and muscle mass, compared to diet alone or high protein diet alone. Patients who engage in regular exercise at initiation and throughout their treatment have the best chances of preserving lean body mass and maintaining loss of fat mass.
Concerns and Future Research on GLP-1 for Weight Loss
There's concern in the general public about how weight loss drugs affect muscle mass, but the presenters emphasize that the data doesn't show GLP-1 analogs have a unique, high level of lean body mass loss compared to other weight loss paradigms.
"We're not used to having successful weight loss outcomes at the scale we've seen with GLP-1 analogs, other than with bariatric surgery. Having concerns about lean body mass is reasonable, but GLP-1s are one tool of many for weight loss," says Dr. Yerevanian. "It's important to allay fears and provide reassurance that some lean body mass loss is a part of the weight loss journey, and we have tools to help."
In addition, the study of how weight loss impacts the functionality of muscle is ongoing.
"This is an area of active investigation. We don't entirely know the full detail of what the muscle physiology is in active weight loss," says Dr. Yerevanian. "Just because a patient has measured decreases in lean body mass and fat-free mass, doesn't necessarily mean that the functional status of the muscle is worse."
The presenters also note that bone loss may be more of a concern with certain patients, such as older women and those with frailty, so more functional testing may be necessary before initiating GLP-1 treatment in these patients. They emphasize that more functional studies on bone and muscle loss is needed, particularly in older patients.