Drugs known as GLP-1 medications have helped many people lose large amounts of weight.
These drugs, including popular names like Ozempic and Wegovy, are now widely used by people with obesity, type 2 diabetes, and even heart failure.
While the weight loss they cause brings several health benefits—such as better blood sugar control, improved short-term heart and kidney health, and even longer survival—new research suggests something may be missing.
Experts at the University of Virginia have raised concerns that these drugs do not improve cardiorespiratory fitness, also known as CRF, which is a major marker of long-term health.
CRF is a way to measure how well the heart, lungs, muscles, and blood vessels work together during exercise. It gives doctors a strong clue about a person’s risk of dying from heart disease or other causes. In fact, high CRF is more important than body weight when it comes to predicting life expectancy.
One of the researchers, Dr. Zhenqi Liu, said some patients taking GLP-1 drugs reported feeling like they were losing muscle. This matters because muscles—especially those that help with posture and movement—are key to staying active, independent, and healthy. Losing too much muscle can raise the risk of health problems and lower quality of life.
Although GLP-1 drugs help people lose body fat, they also cause loss of fat-free mass, which includes muscle. Studies show that 25% to 40% of the total weight lost on these drugs is fat-free mass. In comparison, people usually lose only about 8% of fat-free mass per decade due to aging.
Dr. Liu, along with graduate student Nathan Weeldreyer and exercise physiologist Dr. Siddhartha Angadi, reviewed existing research to understand the impact of these drugs on CRF.
They found that while GLP-1 drugs do improve some heart functions, they do not lead to noticeable improvements in VO2max, the main measure of CRF. VO2max shows how much oxygen the body can use during intense physical activity and is considered a gold-standard measure of heart and lung fitness.
For people with obesity, CRF is often low to begin with. Some have low CRF due to too little muscle, while others have muscles that don’t work well because of fat inside the muscle tissue. This makes it important to protect and improve muscle quality during weight loss.
The team points out that a few small studies suggest that exercise might help improve CRF in people taking GLP-1 drugs, but more research is needed to confirm this.
They stress the importance of combining these medications with exercise and good nutrition to avoid losing too much muscle. They also suggest that future drug treatments may include added support to protect muscle, such as monoclonal antibodies, which are already being studied.
In the meantime, they recommend doctors talk with patients about ways to keep muscle mass while using GLP-1 medications. This includes screening for signs of low muscle or poor nutrition before starting the drugs, encouraging regular exercise, and making sure patients get enough protein in their diet.
Exercise during GLP-1 treatment, they say, could help protect or even improve VO2max—but this still needs to be tested in larger studies. The team hopes their findings will encourage more research and better care for people using these medications.
Their paper was recently published in the Journal of Clinical Endocrinology & Metabolism (JCEM).
If you care about weight loss, please read studies about Scientists find secrets to long-term weight loss success and findings of Weight loss surgery linked to this mental disease.
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