Effect of treatment with receptor agonists on muscle mass

New studies show that pharmacological treatment with GLP-1-RA and dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GIP-RA) cause almost as much weight loss as gastric surgery. However, there are concerns that greater weight loss could have a negative impact on muscle mass, especially in more susceptible patients. Therefore, it is important to find out whether changes in the muscles from weight loss treatments such as GLP-1 RAs are negative for the muscles (maladaptive), a normal response to weight loss (adaptive), or even improve muscle health or function. Andreas Birkenfeld, DZD spokesperson and Director of the Helmholtz Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the University of Tübingen, describes it as follows: “The concept of adaptive muscle adjustment is known from the heart. With high blood pressure, the heart muscle has to pump harder and the heart muscle thickens, meaning that the heart mass increases. If the blood pressure is lowered, e.g. with medication, the heart muscle becomes thinner again and the mass decreases because it no longer has to exert as much force. This process is positive for the heart muscle and is characterized as adaptive. It is also known that the muscle mass that a heavy person needs to support him- or herself decreases when the person loses weight and the muscle no longer has to carry the same weight. This process is also generally considered to be adaptive.” How this is to be classified in the context of treatment with GLP-1 RAs, such as semaglutide or tirzepatide, is discussed in the new article in 'Circulation'.

Weight loss through GLP-1 RAs has an adaptive effect on the muscles

In order to answer this question, current findings and additional studies using magnetic resonance imaging, which provide more precise findings than previous methods of measuring muscle volume, are included. These indicate that the skeletal muscle changes in GLP-1 RA treatments are a normal, adaptive process. The changes in muscle volume correspond to expectations based on age, health status and weight loss. In addition, weight loss in persons with obesity leads to improved insulin sensitivity and less fat in the muscles, thus improving muscle quality. The quality improvement of the muscles is the important criterion for judging whether a process is positive or negative for the muscles. Better muscle quality is associated with a lower risk of loss of strength and function or even increases strength and function.

However, factors such as advanced age and pre-frailty can influence the selection of patients that are eligible for these therapies. Several pharmacological treatments to maintain or improve muscle mass in combination with GLP-1-based therapies are in development for these patients.

More objective methods needed to assess muscle health

The authors emphasize that the introduction of more objective and comprehensive methods to assess muscle health is crucial for the future development of GLP-1-based and other weight loss therapies and for patient-centered treatment optimization. This includes accurate and meaningful assessments of muscle quantity, composition, function, mobility and strength.

It is important that patients and doctors understand how the medication used affects muscle mass. With their article, the three authors therefore want to bring clarity to the current discussion. They say that this is important because it is foreseeable that many more patients will use these drugs in the future.
 

Original publication:
Jennifer Linge, Andreas L. Birkenfeld, Ian J. Neeland: Muscle Mass and Glucagon-Like Peptide-1Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss? Circulation. 2024;150:00–00. DOI: 10.1161/CIRCULATIONAHA.124.067676