Tag: cachexia

Skeletal Muscle Health Amid Growing use of Weight Loss Medications

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A recent commentary published in The Lancet highlights the critical importance of skeletal muscle mass in the context of medically induced weight loss, particularly with the widespread use of GLP-1 receptor agonists. These medications, celebrated for their effectiveness in treating obesity, have raised concerns regarding the potential for substantial muscle loss as part of the weight loss process. 

Dr Steven Heymsfield, professor of metabolism and body composition, and Dr M. Cristina Gonzalez, adjunct professor in metabolism-body composition, both of Pennington Biomedical Research Center joined colleagues Dr Carla Prado of the University of Alberta, and Dr Stuart Phillips of McMaster University on authoring the commentary, titled “Muscle Matters: The Effects of Medically Induced Weight Loss on Skeletal Muscle.”  

The authors emphasise that muscle loss, as measured by decreases in fat-free mass, can account for 25 to 39% of total weight lost over a period of 36 to 72 weeks. This rate of muscle decline is significantly higher than what is typically observed with non-pharmacological caloric restriction or normal aging and could lead to unintended negative health consequences. 

Despite the promising metabolic benefits associated with GLP-1 receptor agonists, including improvements in fat-to-fat-free tissue ratios, the potential adverse effects of muscle loss are gaining attention. Skeletal muscle plays critical roles not only in physical strength and function but also in metabolic health and immune system regulation.  

A decline in muscle mass has been linked to decreased immunity, increased risk of infections, poor glucose regulation, and other health risks. The authors suggest that muscle loss due to weight reduction may exacerbate conditions like sarcopenic obesity, which is prevalent among individuals with obesity and contributes to poorer health outcomes, including cardiovascular disease and higher mortality rates. 

While the short-term effects of muscle loss on physical strength and function remain unclear, the commentary calls for future research to explore how reductions in muscle mass might improve muscle composition and quality. The authors stress the need for a multimodal approach to weight loss treatment, combining GLP-1 receptor agonists with exercise and nutritional interventions to preserve muscle mass. 

“We have to be mindful of the side effects that we are seeing with the new weight loss medications, such as a person eating less while on the medications and not getting the appropriate amount of dietary vitamins and minerals,” Dr Heymsfield said. “Also, when a person loses weight, they are not only losing fat, they also lose muscle. We are looking at how that muscle loss can be better managed with consumption of an adequate amount of protein along with an optimum amount of exercise.” 

This evolving conversation underscores the importance of ensuring that weight loss interventions promote overall health, including muscle preservation, as part of a comprehensive strategy for treating obesity. 

For more information, please refer to the full commentary in The Lancet at https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00272-9/fulltext.  

Source: Pennington Biomedical Research Center

New Trial of Drug Shows Promise in Combating Cancer-caused Cachexia

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Researchers discovered a drug that safely and effectively helped cancer patients when they suffered from cachexia, a common condition related to cancer that involves weight loss and muscle wasting.

The results of the randomised phase 2 clinical trial, which included 187 individuals who experienced cachexia with pancreatic (32%), colorectal (29%) or non–small-cell lung (40%) cancer, appear in the New England Journal of MedicineRichard Dunne, MD, MS, a Wilmot Cancer Institute oncologist and cachexia expert was part of the large group of investigators who ran the nationwide clinical trial.

Cachexia involves loss of appetite and weight, muscle-wasting, fatigue, and weakness. It affects more than 50% of people who have cancer, and currently there are no FDA-approved treatments.

Scientists discovered that the monoclonal antibody ponsegromab blocks a hormone known as GDF-15 that regulates appetite and body weight. The patients in the trial had elevated levels of GDF-15, a primary driver of cachexia, and ponsegromab improved many aspects of cachexia and its symptoms.

Patients were randomised to receive ponsegromab at doses of 100mg, 200mg, or 400 mg, or to receive placebo. At 12 weeks, patients in the ponsegromab groups had significantly greater weight gain than those in the placebo group, with a median between-group difference of 1.22 kg in the 100mg group, 1.92 in the 200mg group, and 2.81 in the 400mg group. Improvements were observed across measures of appetite and cachexia symptoms, along with physical activity, in the 400mg ponsegromab group relative to placebo.

Drugmaker Pfizer supported the study, and released this news. Side effects were minimal, Dunne said, and in fact ponsegromab appeared to be safer than common appetite stimulants used by cachexia patients.

“This is super exciting,” said Dunne, an associate professor of Medicine at the University of Rochester Medical Center. “This study is an important step in providing treatment for the hundreds of thousands of patients who suffer from poor quality of life due to cachexia.”

Several academic medical centres participated in the clinical research, which was led by John D. Groarke, MB, BCh, MPH, at Pfizer. Investigators are continuing to study GDF-15 and the importance of the biomarker in several types of cancer. Other clinical trials are also testing additional cachexia treatments that do not target the GDF-15 pathway.

Source: University of Rochester Medical Center