Glucagon-like peptide-1 (GLP-1) receptor agonists, more commonly known as GLP-1 drugs or GLP-1s, have skyrocketed in popularity, with usage up nearly 600 percent over six years, according to a report from FAIR Health. Originally approved for the treatment of type 2 diabetes, these drugs are now largely used as a weight loss aid. As weight loss drugs, they’re certainly effective, with many users achieving “clinically significant” weight loss. But new research materials from University of Virginia (UVA) experts suggest that GLP-1s fall short of “miracle drug” status. The UVA experts found that GLP-1 drugs fail to improve heart and lung function, and may also drive harmful muscle loss. The paper was published in The Journal of Clinical Endocrinology & Metabolism (JCEM).
Weight Loss Drugs and Cardiovascular Health
Led by UVA researcher Zhenqi Liu, the paper explains that GLP-1 drugs drive fat loss — but they may not improve other key markers of health. This includes cardiovascular health, a major indicator of mortality risk. The drugs may also drive the loss of “fat-free mass,” including muscle.
Reviewing Weight Loss Drug Data
To get a more holistic picture of the potential long-term consequences of GLP-1 drugs, Liu and his collaborators first reviewed available data on the drugs’ effects on cardiorespiratory fitness, or CRF. CRF, also known as VO2 max, measures how well the body can use oxygen during exercise. It also helps doctors predict patients’ risk of cardiovascular mortality.
Why review the CRF of patients using GLP-1 drugs? The answer is simple: Patients with obesity often have low CRF. In fact, the UVA experts noted that CRF was actually a better indicator of mortality risk than “overweight or obesity status,” adding, “Once CRF was factored in, body weight failed to predict the risk of mortality.” Thus, the UVA team wanted to know: In treating obesity, could GLP-1 drugs also improve patients’ CRF?
GLP-1s and Positive Health Outcomes
Upon reviewing available medical literature, the researchers learned that the short answer was “no.” While GLP-1 drugs did improve certain measures of heart function, those improvements didn’t translate into notable CRF improvements.
Even more concerning, the drugs were found to drive muscle loss in patients who experienced rapid weight loss. “Some patients literally told me that they felt that they were losing muscle or muscle was slipping away from them while they were on [GLP-1] medications,” said Liu in a university news release, calling the loss of muscle mass a “serious concern.” Liu added: “Muscle, especially axial muscle, is essential for posture, physical function and overall well-being. Losing lean body mass can increase the risk of cardiovascular disease, all-cause mortality and diminished quality of life.”
The researchers ultimately concluded that GLP-1 drugs “significantly reduce body weight and adiposity, along with a substantial FFM [fat-free mass] loss.” The drugs also show “no clear evidence of CRF enhancement.”
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Does this research suggest that individuals with obesity should avoid GLP-1 drugs? Not necessarily. However, Liu wrote in the news release that “it is important that patients prescribed GLP-1 drugs have conversations with their health care providers about strategies to preserve muscle mass.” Patients using these drugs may also need to prioritize both aerobic exercise and strength training to preserve muscle mass and promote long-term health.
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