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Strength training and GLP-1

This is an excerpt from Smarter Workouts 2nd Edition by Pete McCall.

Originally developed as a treatment for type 2 diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications that help promote weight loss and are now being prescribed as a means of treating obesity to help individuals achieve a healthy body weight. GLP-1s have been successful in promoting significant weight loss; however, according to the research literature, anywhere from 30 to 50 percent of that weight can come from lean muscle mass. The good news is that GLP-1 drugs can facilitate weight loss; however, because it can occur at the expense of muscle tissue, it is necessary to perform strength training to maintain lean mass while taking the drugs.

GLP-1s include drugs such as semaglutide (sold under the brand names Ozempic and Wegovy) and tirzepatide (Mounjaro and Zepbound are the most popular brands). These agents mimic the action of the endogenous incretin hormone GLP-1, enhancing insulin secretion and inhibiting glucagon release in a glucose-dependent manner. Beyond glycemic control, GLP-1s have demonstrated powerful effects on satiety and weight loss. GLP-1s promote weight loss through multiple mechanisms: they reduce appetite, slow gastric emptying, and improve insulin sensitivity. They represent a breakthrough in treating obesity, yet they are not without risks—chief among them is the potential for muscle loss because rapid weight loss can often result in a loss of both fat AND muscle tissue. Carbohydrates consumed in the diet are stored in type II muscle cells as glycogen to be metabolized into ATP to fuel activity; a GLP-1 could affect normal carbohydrate metabolism, resulting in a loss of muscle tissue while taking the drugs.

Strength training provides a vital countermeasure, preserving lean body mass and ensuring that weight loss is healthy, sustainable, and functional. Because muscle is essential for optimal metabolic health and physical function, it is important to preserve muscle tissue while exercising to lose unwanted weight. GLP-1 drugs promote weight loss in the following ways:

• Appetite suppression: GLP-1s act on the hypothalamus, particularly the arcuate nucleus, reducing appetite and increasing satiety (van Can et al. 2014).
• Delayed gastric emptying: Slower gastric emptying prolongs the feeling of fullness and reduces caloric intake (Meier 2012).
• Increased insulin sensitivity: Improved glucose metabolism to regulate homeostasis can promote metabolic efficiency, an indirect means of supporting weight loss.
• Reduced food reward signaling: GLP-1s can also influence the mesolimbic dopamine system, decreasing the desire to eat purely for the sake of pleasure (van Bloemendaal et al. 2014).
• Caloric deficit: Collectively, the above effects could result in a significant caloric reduction, creating the necessary energy deficit for weight loss.

Clinical trials of semaglutide and tirzepatide have consistently reported that 20 to 40 percent of the total weight lost may come from lean body mass, including skeletal muscle. In a review of body composition changes, researchers observed that up to 30 percent of weight lost on semaglutide was lean mass (Heymsfield et al. 2023). Likewise, Rosenstock and colleagues noted that research subjects taking tirzepatide experienced greater fat mass reduction than those using semaglutide, but the weight loss included a 25 to 30 percent loss of lean mass (Rosenstock et al. 2021).

Participating in a progressively challenging strength training program while taking GLP-1 agonists promotes muscle protein synthesis, necessary for preserving and growing lean muscle mass; this is essential because muscle mass supports your resting metabolic rate (RMR), the ability to burn calories without performing any activity. A loss of muscle mass could result in a lower RMR, impeding the overall goal of weight loss.

Combining strength training with GLP-1 agonist drugs provides multiple benefits, including preserving muscle mass, enhancing fat loss, improving metabolic health, and supporting cardiovascular health. Should you take a GLP-1, keep in mind that strength training will be necessary to help counterbalance the muscle loss that can occur with rapid weight loss and ensure that you can maintain your strength, physical function, and healthy body composition, during and after weight loss.

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