Grant: Master's Award: Canada Graduate Research Scholarships - Master's program

GLP-1 receptor agonists (GLP-1RAs), such as Ozempic have transformed the ways we treat obesity and other metabolic diseases. Clinical trials show that these drugs are effective for weight loss and are used by hundreds of thousands of Canadians. However, these studies also show that up to ~40% of weight lost while taking GLP-1RAs is lean muscle mass instead of fat. This disproportionate loss in muscle can make people functionally weaker, increasing the risk of falls and frailty, reducing overall quality of life. Given that these drugs often cause nausea and lower appetite, eating enough protein to protect muscle is also difficult. In all, the relative risks of GLP-1RAs remain a subject of debate with little research exploring the mechanisms behind muscle loss. Scientists and clinicians are yet to understand why GLP-1RAs cause this loss in muscle. That said, we believe that the answers may lie in how these drugs change the way muscle cells use and produce energy. Mitochondria, the ‘powerhouse of the cell’, burn different fuels such as sugars, fats, or amino acids to produce energy and GLP-1RAs may change which fuels they prefer. Our research will explore how GLP-1RAs affect energy use in muscle by studying platelets, small blood cells that reflect muscle metabolism. Through the measurement of platelet metabolism in mice treated with GLP-1RAs, we can detect changes that mirror changes in muscle, providing a simple ‘liquid biopsy’ for muscle heath. Understanding how GLP-1RAs alter muscle metabolism will help explain why people lose muscle while taking these medications and how to prevent it. This knowledge will support the development of safer, next-generation GLP-1RAs that promote healthy weight loss while preserving muscle mass, strength, and quality of life.