GLP-1 receptor agonists, including semaglutide (Ozempic, Wegovy), liraglutide, dulaglutide, and tirzepatide, are currently considered among the most effective pharmacotherapies for the management of obesity. However, new research presented at ENDO 2026 (the Annual Congress of the Endocrine Society) indicates that patients undergoing treatment with these agents may experience a significant decline in physical activity, which could negatively impact long-term therapeutic outcomes.
To evaluate the dynamics of physical activity during GLP-1 therapy, researchers at HSHS St. John’s Hospital in Illinois, led by Dr. Sajana Maharjan, conducted a retrospective observational study. The analysis utilized data from the U.S. National Institutes of Health (NIH) research program, integrating clinical patient information with data from wearable fitness trackers. The study cohort consisted of 753 adults diagnosed with obesity (mean age: 52.7 years; predominantly female) who were undergoing treatment with GLP-1 agonists.
The study authors emphasize that weight loss during treatment with these agents may occur not only through the reduction of adipose tissue but also through the depletion of lean muscle mass. Consequently, regular physical activity—particularly resistance training—is considered an essential component of treatment to maintain muscle mass, strength, and metabolic health.
The researchers compared physical activity metrics before and after the initiation of GLP-1 agonist therapy. The analysis revealed that the average daily step count decreased from 5,047 to 4,487, while the average daily duration of moderate-to-vigorous physical activity declined from 28 minutes to 22 minutes. The most pronounced reductions in physical activity were observed in male patients and those reporting musculoskeletal pain. Notably, factors such as age, heart failure, and a history of stroke did not demonstrate a statistically significant influence on changes in physical activity levels.
Dr. Maharjan stated that, contrary to the expectation that weight loss would incentivize a more active lifestyle, the study failed to confirm such a trend. She posits that these results underscore that physical activity during GLP-1 therapy is not merely an auxiliary recommendation but a mandatory component of treatment. Therefore, medication must be accompanied by targeted interventions to assist patients in maintaining their physical activity levels.
Obesity management specialist Dr. Peter Balazs explained that weight loss does not automatically equate to increased physical activity. He noted that in the context of caloric deficit, the body enters a “conservation mode,” which facilitates a decrease in energy expenditure and a slowing of metabolic processes. Furthermore, side effects associated with GLP-1 agents, such as nausea, fatigue, and gastrointestinal discomfort, may diminish both patient motivation and the capacity for regular exercise.
Dr. Balazs suggests that GLP-1 therapy should be integrated with resistance training, daily walking, and other aerobic activities. Without sufficient physical activity, weight loss may largely result from muscle mass reduction, which negatively affects metabolic health and long-term treatment outcomes. Furthermore, the type, intensity, and timing of exercise must be tailored individually based on the patient’s health status, body mass index (BMI), functional capacity, and injury risk.
Contrasting these findings, New York-based internist Dr. Amanda Kahn notes that in her clinical experience, weight loss frequently encourages patients to adopt a more active lifestyle and pay closer attention to their health. Dr. Kahn suggests that the success of GLP-1 therapy is largely determined by diligent patient monitoring and comprehensive support.
According to Dr. Kahn, when GLP-1 agents are prescribed in the context of a balanced diet, adequate protein intake, exercise, and regular medical supervision, patients not only achieve effective weight loss but also maintain muscle mass, improve physical capabilities, and increase their motivation to maintain an active lifestyle. In her practice, if a patient exhibits significant fatigue, an inability to exercise, insufficient protein intake, or significant muscle loss, the treatment regimen is reassessed or the dosage is adjusted.
The authors note several limitations to the study. As a retrospective observational study, the results reflect statistical associations rather than causal relationships. Additionally, the cohort consisted primarily of middle-aged women, limiting the generalizability of these findings to other populations. Furthermore, the study did not evaluate participants’ exercise habits, motivation levels, or the potential impact of physician-provided counseling on physical activity and lifestyle.
The researchers conclude that the data highlights that GLP-1 agonist therapy should not be limited to pharmacological intervention alone. Modern clinical practice necessitates a comprehensive approach to patient management, including adequate protein intake, regular physical activity, and continuous medical monitoring. This strategy promotes weight loss primarily through adipose tissue reduction while preserving muscle mass, enhancing functional performance, and protecting metabolic homeostasis.
Source: nypost.com
