Dr Nick Fuller
Leading Obesity Expert at the University of Sydney and founder of Interval Weight Loss.
Semaglutide has quickly become a popular option for weight loss, with studies showing it can help people shed up to 15% of their body weight. But alongside fat loss, there's growing concern about losing something else that's essential—muscle.
Maintaining muscle is key to staying strong, energised, and metabolically healthy. This article explores how semaglutide affects your body, the signs of muscle loss to watch for, who’s more vulnerable, and how you can take steps to preserve muscle while on your weight loss journey.
Semaglutide is a medication originally developed to help manage type 2 diabetes, but it has gained wide attention for its powerful effects on weight loss. It works by mimicking a hormone in the body called GLP-1 (glucagon-like peptide-1), which helps regulate blood sugar levels, slow down digestion, and reduce appetite.
By making you feel full sooner and for longer, semaglutide helps reduce overall calorie intake without the need for strict dieting. According to a 2021 study published in The New England Journal of Medicine, participants who took semaglutide lost an average of 14.9% of their body weight over 68 weeks, which was significantly more than those who received a placebo.
Semaglutide also affects areas of the brain involved in hunger and food cravings, helping many people feel more in control of their eating habits. While these effects are beneficial for weight loss, they can also lead to unintentional loss of lean muscle mass, especially if proper diet and activity aren’t maintained alongside the medication.
Learn more about how semaglutide supports weight loss in our article What Is Semaglutide and How Does It Work for Weight Loss?
While semaglutide can support significant weight loss, it’s important to watch for signs that you may also be losing muscle along the way. Here are the signs to watch out for, both subtle and more obvious, that may indicate a drop in lean muscle mass.
One of the earliest signs of muscle loss is a noticeable decline in strength, both in everyday tasks and structured workouts. You might find that carrying groceries, climbing stairs, or even standing for extended periods feels more strenuous than usual. At the gym or during home workouts, you may struggle to lift weights you previously managed or notice your endurance slipping.
This weakening is more than just fatigue; it often reflects a reduction in lean body mass. A systematic review of clinical trials published between 2016 and onwards found that in some studies, up to 40% of total weight lost with semaglutide came from lean mass, including muscle. While fat loss accounted for most of the weight reduction, the findings raised concerns about potential muscle loss, particularly in larger trials. That’s why it’s important to pay attention to physical strength, not just the number on the scale. As muscle supports posture, mobility, and metabolism, a drop in strength can quickly lead to other challenges.
As muscle mass declines, you may begin to feel persistently tired, even if you're eating well and sleeping enough. Muscle tissue plays a key role in energy production and physical stamina. When it's reduced, your body must work harder to perform basic movements, which can leave you feeling drained throughout the day.
This fatigue often builds on the earlier signs of weakness, which makes everyday life feel more taxing. In some cases, people report feeling like they’ve lost their ‘get-up-and-go’, even if they’re excited about their weight loss progress. This combination of low energy and reduced strength can start a downward cycle where you move less, lose more muscle, and feel even more fatigued.
Another sign that muscle is being lost alongside fat is when your body weight drops, but your shape doesn’t noticeably change. If clothes fit looser but your frame appears soft rather than toned, it could be a red flag. This phenomenon happens when fat loss is accompanied by muscle breakdown, leading to reduced definition and firmness.
Preserving lean mass during weight loss is essential for improving body composition, metabolic function, and long-term weight maintenance. Without this balance, the weight loss achieved with semaglutide may not lead to the desired physical results or health benefits.
If your skin appears looser or your limbs feel less firm, it could indicate a loss of muscle tone beneath the surface. This is particularly common in areas like the arms, abdomen, and thighs. While some sagging can result from rapid fat loss alone, the effect is often more pronounced when muscle is also lost, as there's less underlying structure to support the skin.
This change in body firmness tends to follow the earlier signs of low energy and strength loss. Together, they highlight how semaglutide, while effective at reducing weight, can lead to an overall decrease in body quality if not paired with muscle-preserving strategies.
Muscle is metabolically active tissue, meaning it burns calories even at rest. When muscle mass decreases, so does your resting metabolic rate (RMR). This can make it harder to continue losing weight or maintain the loss, since your body now requires fewer calories to function.
Research suggests that during weight loss, skeletal muscle undergoes metabolic adaptations that reduce energy expenditure, even when muscle mass is preserved. This lowered calorie burn, driven by increased mitochondrial efficiency, may contribute to the heightened risk of weight regain. In other words, without enough muscle, your body becomes less efficient at burning calories, making it easier for fat to return once the medication is stopped or slowed.
While muscle loss can affect anyone using semaglutide, certain groups are more vulnerable than others. Belonging to one of these categories may mean your body is more prone to losing muscle during weight loss, making it especially important to take steps to protect your strength and overall health.
Adults over 60: As we age, the body naturally begins to lose muscle mass, a condition known as sarcopenia. Older adults already face a decline in strength and mobility, and adding rapid weight loss from semaglutide can accelerate this process if not carefully managed.
People with low-protein diets: Protein is essential for maintaining and rebuilding muscle. If your daily intake is too low, especially while losing weight, your body may break down muscle for energy. This is particularly risky when using semaglutide, as reduced appetite may make it harder to meet nutritional needs.
Those who do not exercise: Physical activity, especially resistance or strength training, is crucial for preserving muscle during weight loss. Without regular movement, the body has little reason to maintain lean muscle, making it easier for muscle tissue to shrink over time.
People losing weight too quickly: Rapid weight loss can lead to a higher percentage of lean mass loss. Slower, steady weight loss allows the body to better preserve muscle, while quick drops in weight, which are common with semaglutide, can result in both fat and muscle reduction if not monitored.
Individuals with chronic illness: Certain conditions like diabetes, cancer, or inflammatory diseases can increase the risk of muscle wasting. When combined with a medication like semaglutide, these individuals may need closer supervision to prevent further muscle breakdown.
Those who skip meals often: Skipping meals can lead to insufficient calorie and protein intake, forcing the body to use muscle for fuel. This pattern, especially when paired with reduced appetite from semaglutide, can compound the risk of losing valuable lean mass.
People with low body mass to start: If you already have a low body weight or minimal muscle mass, you may be more susceptible to muscle loss. With less muscle to begin with, even small reductions can significantly impact your strength, posture, and energy levels.
Losing fat may be the goal, but when it comes with a drop in muscle mass, the results can be less than ideal. Here are the potential side effects of losing muscle during weight loss with semaglutide:
Muscle burns more calories at rest than fat, so losing it can reduce how many calories your body uses daily. A study found that people who lost weight through calorie restriction alone also lost lean mass and aerobic capacity, both of which contribute to a lower metabolic rate. In contrast, those who exercised during weight loss maintained more muscle and metabolic function. This highlights the importance of muscle-preserving strategies when using semaglutide, as losing lean mass could make it harder to maintain weight loss long term.
When weight is regained after dieting, fat often returns while lost muscle does not, suggesting that muscle loss during dieting may contribute to future fat regain. Regaining fat without rebuilding muscle can make your body composition worse than before you started treatment.
Your muscles help stabilise your spine and joints. When strength in the core, back, or shoulders declines, posture and alignment suffer, often leading to pain or discomfort. Research indicates that weak trunk muscles are linked to low back pain and poor balance, increasing the risk of falls and injury. Another study found that core weakness raises spinal stress during movement, making injury more likely. Simply put, strong muscles aren’t just for looks; they help you stay upright, balanced, and pain-free.
As muscle mass decreases, so does functional strength, but not always in a 1:1 ratio. A study on older adults shows that strength tends to decline faster than muscle size alone would explain, likely due to a drop in muscle quality. That means even modest muscle loss, such as that reported in some semaglutide users, can have a larger-than-expected impact on your ability to move, lift, and stay active.
Muscle weakness, particularly in the legs and core, can impair balance and coordination, increasing the risk of falls and injuries. This is especially well-documented in older adults, where reduced strength is a leading predictor of falls. While semaglutide-related muscle loss hasn't been shown to directly cause falls, any drop in strength can raise the risk of sprains, strains, or more serious injuries during physical activity.
Losing weight is a positive step toward better health, but it’s important to preserve muscle along the way. Here are practical strategies to help you stay strong while using semaglutide:
Eat enough protein every day:
Protein provides the building blocks your body needs to maintain and repair muscle tissue. Aim for around 1.2 to 2.0 grams of protein per kilogram of body weight per day, depending on your activity level and goals.
Do strength or resistance training:
Incorporating exercises like weightlifting, resistance bands, or bodyweight movements helps signal your body to hold onto muscle. Even just two to three sessions a week can make a meaningful difference.
Stay active through walking or light workouts:
Daily movement matters. Low-impact activities like walking, stretching, or yoga help keep your muscles engaged, improve circulation, and support overall mobility.
Get enough sleep and rest:
Muscle recovery happens during rest, particularly during deep sleep. Aim for at least 7–9 hours of quality sleep per night to allow your muscles to repair and grow stronger.
Avoid skipping meals:
Consistently missing meals can lead to insufficient calorie and protein intake, forcing your body to break down muscle for energy. Try to eat balanced meals at regular intervals, even if your appetite is lower due to semaglutide.
Semaglutide can be an effective tool for weight loss, but it’s important to understand the potential impact on your muscle mass. While fat loss is often the focus, losing muscle along the way can affect your strength, energy, metabolism, and overall health.
The good news is that muscle loss isn’t inevitable. By staying mindful of your nutrition, maintaining an active lifestyle, and listening to your body, you can take steps to protect your lean mass and support long-term results. If you’re unsure how to balance your goals, speak with a healthcare provider or dietitian for personalised advice.
Remember, healthy weight loss isn’t just about the number on the scale; it’s about preserving your strength, function, and well-being along the way.
Dr Nick Fuller is the founder of Interval Weight Loss and is a leading obesity expert at the University of Sydney with a Ph.D. in Obesity Treatment. Dr Fuller is also the author of three best-selling books and his work been published in top ranked journals in the medical field, including JAMA, Lancet and American Journal of Clinical Nutrition.