Ozempic and the Weight Loss Trade-Off. What Are You Really Losing?

By now, most people are familiar with the popular diabetes-turned-weightloss drugs, semaglutide, more commonly known by their brand names, Ozempic and Wegovy. The use of social media and celebrity endorsement has fueled a dramatic increase in the use of semaglutide injections for weight loss, and far from being an internet trend that comes and goes, semaglutide has become a staple in many American households. By 2021, more than 2 million people were using semaglutide injections from 600,00 in 2019. With an estimated 129.2 million U.S. adults eligible for semaglutide specifically for weight management, this increase is largely driven by the drug’s growing use for weight loss, and demand has only continued to rise. By 2024, 1 in 8 Americans—roughly 12% of the population—were using semaglutide, highlighting its rapid adoption nationwide. 

Semaglutide promotes weight loss through several mechanisms. The drug acts on receptors in the brain to reduce appetite and increase satiety, it delays gastric emptying helping prolong feelings of fullness, and it modulates blood sugar and insulin to control cravings. This multipronged approach has shown to work incredibly well, with the average semaglutide user losing 15% of their body weight in 6-12 months. For individuals who struggle with weight loss, this can sound like a "miracle drug", but is there a catch? 

The key issue is the type of weight being lost—because that 15% reduction in body mass includes not only fat, but also lean mass. Lean mass generally refers to everything in the body except fat, including muscles, bones, organs, and other fat-free tissues. When lean mass declines, it increases the risk of sarcopenia, a condition common in older adults marked by the gradual, widespread loss of muscle mass and strength resulting in frailty. To minimize these negative outcomes, it's important to focus on losing fat while preserving lean mass during weight loss efforts. 

Although semaglutide primarily reduces fat mass, some studies have reported up to 39% of total weight loss as coming from lean mass. To compare, humans lose 3-8% of muscle mass per decade after the age of 30, causing some scientists express concern over the accelerated rate of lean mass loss with semaglutide.  It is important to note that any rapid weight loss, even without semaglutide, can lead to a loss of lean mass. This is why healthcare professionals promote sustained lifestyle changes such as healthy eating and exercise over crash diets. 

Whether the reduction in lean mass is greater with semaglutide when compared to traditional weight loss methods is currently contested. Some evidence suggests that longer treatment duration is positively correlated with lean mass reduction, while shorter-term studies reporting mostly fat reduction. Further studies are needed to understand the long-term effects of semaglutides in weight management and metabolic health. 

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