Glucagon-like peptide-1 (GLP-1) receptor agonist drugs, such as the much publicised Ozempic, can transform weight loss for those classed as obese. However, research shows these drugs do not improve a critical measure of health: cardiorespiratory fitness.
These medications help people shed fat, yet they also strip away vital muscle mass. This has led to academic concerns regarding long-term heart health, physical function, and mortality.
Researchers from the University of Virginia Health System urge combining treatment with exercise, protein intake, and possibly future drugs to avoid these ‘hidden’ downsides of rapid weight loss.
GLP-1: Risks and benefits
GLP-1 drugs have clear health benefits for people with obesity, type 2 diabetes and heart failure, including improving blood-sugar control, short-term cardiorenal benefits and improvements in survival outcomes.
That said, medics need to consider recommending exercise programs or develop other approaches, such as nutrition supplements or complementary medications, to help GLP-1 patients get the full cardiorespiratory benefits of substantial weight loss over the long-run, the researchers say.
GLP-1 drugs help people lose fat yet this also involves the loss of fat-free mass, of which muscle makes up 40% to 50%. Fat-free mass lost accounts for 25-40% of the total pounds lost, while age-related declines in fat-free mass are only 8% per decade.
Muscle mass loss
According to lead researcher Zhenqi Liu: “Some patients literally told me that they felt that they were losing muscle or muscle was slipping away from them while they were on these medications. This is a serious concern. 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. We need to make sure that patients prescribed these medications aren’t already at risk for malnutrition or low muscle mass.”
Risk: Cardiorespiratory fitness
Cardiorespiratory fitness (CRF) is a potent predictor of all-cause and cardiovascular mortality risk across a range of populations, including obesity, diabetes and heart failure. CRF is a measure of how well the body can use oxygen during exercise. It is a handy way for doctors to assess how well the heart, lungs, muscle and blood vessels work together, and it is used to predict all-cause and cardiovascular mortality (risk of death).
Patients with obesity often have low CRF. In some cases, this is because the person lacks muscle mass; in others, a person may have enough muscle, but the quality of that muscle is compromised by fat that has penetrated it.
GLP-1 drugs improve certain measures of heart function, yet those improvements don’t translate into significant improvements in CRF.
The researchers remain concerned that this could take a toll on patients’ metabolic health, healthspan/frailty and overall longevity. They are urging additional research to better understand the effects of the drugs and ensure patients get the best possible outcomes.
The research appears in The Journal of Clinical Endocrinology and Metabolism, titled “Incretin Receptor Agonism, Fat-free Mass, and Cardiorespiratory Fitness: A Narrative Review.”
