New publications
GLP-1 drugs fail to provide key long-term health benefits
Last reviewed: 27.07.2025
All iLive content is medically reviewed or fact checked to ensure as much factual accuracy as possible.
We have strict sourcing guidelines and only link to reputable media sites, academic research institutions and, whenever possible, medically peer reviewed studies. Note that the numbers in parentheses ([1], [2], etc.) are clickable links to these studies.
If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please select it and press Ctrl + Enter.
Popular GLP-1 drugs help many people lose significant amounts of weight, but they don't provide the key improvements in heart and lung function needed for long-term health, University of Virginia experts warn in a new paper.
The researchers highlight that GLP-1-related weight loss has many clear benefits for people with obesity, type 2 diabetes and heart failure, including improved blood sugar control, short-term cardiorenal benefits and improved survival.
But doctors may consider recommending exercise programs or developing other approaches, such as nutritional supplements or additional medications, to help patients on GLP-1 get the full cardiorespiratory benefits of significant weight loss over the long term, the researchers say.
“Some patients have literally told me that they feel like they’re losing muscle mass or that their muscle is going away with these drugs,” said study researcher Zhengqi Liu, MD, professor of medicine and the James M. Moss Professor of Diabetes Medicine at the University of Virginia School of Medicine and former chief of the division of endocrinology and metabolism at UVA Health.
“This is a serious problem. Muscle, especially axial muscle, is important for posture, physical function, and overall well-being. Losing lean body mass can increase the risk of cardiovascular disease, all-cause mortality, and poor quality of life. We need to make sure that patients who are prescribed these drugs are not already at risk for malnutrition or low muscle mass.”
About GLP-1 drugs
While GLP-1 supplements help people lose fat, they also lose lean mass, which accounts for 40-50% of muscle tissue. In fact, lean mass accounts for 25-40% of the total pounds lost, while age-related fat-free mass loss typically only averages 8% per decade.
Liu and his co-authors — graduate student Nathan R. Wildreyer and Siddhartha S. Angadi, PhD, an assistant professor of kinesiology in UVA's School of Education and Human Development — wanted to better understand the potential long-term consequences of this muscle loss, so they analyzed the available data on the effects of these drugs on cardiorespiratory fitness (CRF).
CRF (or VO₂max) is a measure of how well the body can use oxygen during exercise. It’s a handy way for doctors to assess how effectively the heart, lungs, muscles, and blood vessels work together, and it’s used to predict all-cause and cardiovascular mortality.
Conclusions of the study
In obese patients, CRF is often low. In some cases, this is due to a lack of muscle mass; in others, a person may have enough muscle, but its quality is compromised by fat intrusion.
“Cardiorespiratory fitness is a powerful predictor of all-cause and cardiovascular mortality risk across a variety of populations, including those with obesity, diabetes, and heart failure,” said Angadi, a cardiovascular exercise physiologist in the UVA Department of Kinesiology.
“In a recent study from our group that looked at mortality rates in nearly 400,000 people worldwide, we found that CRF was a significantly better predictor of mortality risk than being overweight or obese. In fact, after accounting for CRF, body weight no longer predicted mortality risk. That’s why it’s so important to understand the impact of this new class of drugs.”
A review of the available medical literature has shown that GLP-1 drugs improve some measures of cardiac function, but these improvements do not translate into significant improvements in VO₂max.
Some small studies, they note, have suggested that exercise might help improve VO₂max in patients taking GLP-1 drugs, but these studies had weak methodological controls, and larger, higher-quality studies are needed to confirm this.
How to Ensure Healthy Weight Loss
Ultimately, the researchers conclude that GLP-1 supplements “significantly reduced body weight and fat mass along with significant loss of lean mass, but without clear evidence of improvement in CRF.”
They are concerned about the impact this could have on patients’ metabolic health, their active lifespan and their overall lifespan. The scientists are calling for more research to better understand the effects of the drugs and ensure that patients receive the best possible benefits.
However, they note that there are already encouraging signs that drugs may be developed to help, such as a monoclonal antibody that can reverse muscle loss.
“This is an area of active research, and we hope that better solutions will emerge soon,” Liu said.
“But for now, it’s important for patients prescribed GLP-1 drugs to discuss muscle-preserving strategies with their doctors.
The American Diabetes Association recommends screening patients for risk of malnutrition and low muscle mass before starting these drugs and encouraging adequate protein intake and regular exercise throughout treatment.”
“Finally,” Angadi added, “exercise during GLP-1 therapy remains to be evaluated for its ability to maintain or improve VO₂max during treatment.”
The researchers published their findings in the Journal of Clinical Endocrinology & Metabolism.