‘Skinny Fat’ Concerns with Semaglutide: What You Need to Know About Semaglutide Muscle Loss

May 6, 2024
A trainer helping a woman exercise.

Semaglutide, the active ingredient in Ozempic, Wegovy, and Rybelsus, is indisputably a major advance in treating obesity and type 2 diabetes. These glucagon-like peptide-1 (GLP-1) receptor agonists can help individuals lose a remarkable 15-18% of their body weight, translating to as much as 50 pounds for someone with a starting weight of 300 pounds.

However, weight loss does not discriminate between fat loss and muscle loss. Skinny fat or sarcopenic obesity describes a condition in which a person appears thin (or at least at a healthy weight) but has a higher than healthy percentage of body fat with low muscle mass. Even with a healthy body mass index (BMI), having a ‘skinny fat’ body composition can put you at increased risk of metabolic issues and chronic diseases. For this reason, the condition is often referred to as metabolically obese, normal weight (MONW).

Understanding Sarcopenic Obesity

MONW does not have a standardized definition, and therefore, it is not used to diagnose a medical condition. Tracking waist circumference is one recommended approach for diagnosing sarcopenic obesity. Unlike BMI, a waist circumference measurement that falls outside of a healthy range is associated with an increase in body fat. The American Heart Association recommends having a waist circumference smaller than 35 inches in women and 40 inches in men.1

Sarcopenic obesity is a related condition. It refers to an age-related loss of muscle mass and strength (sarcopenia) and an excess accumulation of body fat. Muscle mass declines start around age 40. After age 50, muscle mass declines by 1% to 2% each year.2

Sarcopenic obesity is most commonly found in older adults, but it can occur at any age. The condition requires having both lower muscle mass and higher body fat. It is considered a distinct condition from being overweight or having age-related loss of muscle mass. The combination of lower muscle mass and higher body fat increases the risk of chronic disease more than having either condition alone.

Sarcopenic obesity can lead to a variety of health issues, including reduced physical function, decreased mobility, increased risk of falls and fractures, and a higher susceptibility to chronic diseases like type 2 diabetes, dementia, cancer, and cardiovascular disease.3

An older man exercising.

Risks of “Skinny Fat”

A higher than healthy body fat percentage and low muscle mass can lead to metabolic dysfunction, even if your weight falls within the healthy BMI range. BMI is a tool used to classify someone based on their body weight: healthy if their BMI falls between 18 and 24.9 kg/m2, overweight if it is between 25 and 30, and obese if their BMI is over 30.

Unfortunately, one of the significant drawbacks of using BMI as a tool to diagnose obesity is that it does not distinguish between fat and lean body mass contributions to body weight. A competitive athlete with a high muscle mass may be considered overweight based on their BMI. Likewise, a person with low muscle mass and a high body fat percentage could land in the healthy BMI range.

The BMI formula was developed based on statistics taken from European men. It implies that there is a strong correlation between a person’s height and weight, which is not valid. The formula is less accurate when evaluating the health of women and Black, Hispanic, and Asian populations.

Key health risks from being ‘skinny fat’ include the following: 4

  • Insulin resistance, high cholesterol, and increased risk of type 2 diabetes from having excess belly fat (visceral fat).
  • Increased risk of heart disease and strokes from damage to blood vessels and increased risk of blood clots.
  • Increased inflammation due to chemicals released from metabolically active fat cells.
  • Increased risk of developing fatty liver disease.

Role of Semaglutide

Semaglutide is a synthetic version of the naturally occurring GLP-1 hormone. GLP-1 is produced in the intestines and plays a crucial role in regulating blood sugar levels and appetite. By mimicking GLP-1, semaglutide suppresses appetite, slows gastric emptying, and reduces food cravings, leading to significant weight loss.

Rapid weight loss can also result in semaglutide muscle loss. Using calorie restriction to induce weight loss leads to loss of fat and muscle mass. About one-third of weight loss is lean body mass, with men losing slightly more fat-free mass than women.5  

However, some animal studies and small studies in humans indicate semaglutide may lead to preferential body fat loss, preserving muscle mass more than fat mass.6,7 Other studies indicate that semaglutide can cause a significant decrease in fat-free mass, in the same ratio as weight loss from calorie restriction alone (2/3rds body fat and 1/3rd lean body mass).8,9

There is not enough research to show the potential long-term side-effects of semaglutide use and its impact on muscle mass. However, there is plenty of research that shows that unless you take steps to maintain your muscle mass while losing weight, you will lose muscle mass along with body fat.

Clinical Insights

Muscle is a metabolically active tissue that plays a crucial role in overall health and well-being. It helps maintain a healthy resting metabolic rate, which is essential for long-term weight management. When individuals lose muscle mass during rapid weight loss, their metabolism can slow down, making it increasingly difficult to keep the weight off in the long run.

Maintaining muscle mass is also important for preserving physical function, strength, and mobility, particularly as we age. Sarcopenia can significantly impair an individual’s ability to perform daily tasks, leading to a reduced quality of life and an increased risk of falls and fractures.

Obesity is associated with poor muscle quality, which adversely affects muscle strength. Researchers report that increased body fat is associated with having more fat droplets in muscle tissue. Fatty muscle causes decreased muscle power, strength, and shortening velocity.4

When clinical trials were conducted to test the effectiveness of semaglutide for weight loss, the medication was always prescribed in conjunction with a reduced-calorie diet and exercise plan. This highlights the importance of consuming a balanced, nutritious diet and engaging in regular exercise while taking semaglutide. Medication alone can induce weight loss, but it is not the healthiest approach.  

A man with obesity lying on an exercise mat.

Strategies for Prevention

To mitigate the risk of developing sarcopenic obesity while taking semaglutide or similar weight loss medications, healthcare providers recommend a multi-pronged approach. Dietary amino acids, insulin, and muscle contractile activity regulate the balance between muscle synthesis and breakdown.

Amino acids and dietary protein stimulate muscle synthesis in a dose-dependent manner, up to about 20 grams of protein per meal. Insulin secretion suppresses muscle protein breakdown. Exercise increases insulin sensitivity and increases muscle protein synthesis.4

1. Prioritize Protein Intake

Ensuring adequate protein consumption is crucial during weight loss to help preserve muscle mass. Experts recommend consuming 25–30 grams of protein per meal, which can be achieved by consuming lean meats, poultry, fish, eggs, dairy, legumes, and protein supplements.

Protein intake should be distributed throughout the day. Two studies indicate that consuming protein throughout the day results in more muscle protein synthesis than when it is consumed in a single meal or only after exercise.

Consuming protein throughout the day may prevent muscle loss when taking semaglutide. However, it may adversely affect glucose metabolism.4 If you have type 2 diabetes or insulin resistance, it may be a good idea to meet with a dietician to maximize the benefits of a high-protein diet.

2. Incorporate Strength and Resistance Training

Regular strength and resistance training are essential for maintaining and even building muscle mass during weight loss. Incorporating 2-3 strength workouts per week can help counteract the muscle-wasting effects associated with rapid weight loss.

A progressive resistance exercise training program can help you retain and build muscle.

3. Optimize Sleep and Manage Stress

Healthy, restorative sleep patterns and effective stress management are also important factors in preserving muscle mass. Adequate sleep and low stress levels help regulate the hormones involved in body composition, such as cortisol and growth hormone.


Semaglutide and other GLP-1 receptor agonists are considered a game-changer in weight loss treatment. However, it is important to recognize that they, like all medications, have risks and benefits. One risk of rapid weight loss is sarcopenic obesity, a condition characterized by low muscle mass and high body fat. This type of obesity puts people at an elevated risk for chronic diseases. Semaglutide clinical trials were conducted using a comprehensive approach to obesity treatment. This can help prevent semaglutide muscle loss.

Infographics Semaglutide

Sarcopenic obesity results from muscle loss associated with weight loss. Typically, about one-third of weight loss is muscle mass. To preserve your muscle mass, consume a high-protein diet and incorporate resistance training into your daily schedule.

If you are interested in learning more about weight loss medications, Invigor Medical is a national online wellness clinic that offers a range of medically supervised weight loss programs. After completing a simple online form, select the program you are interested in learning more about. If you meet the medical criteria for that program, you will consult with an Invigor Medical practitioner. If approved for the weight-loss program, an Invigor Medical partner pharmacy will ship your prescription and supplies to your home. Learn more about Invigor Medical’s weight loss programs and how to sign up today.

Author: Leann Poston, M.D.
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