GLP-1, Ozempic and muscle mass – how protein, strength training and creatine can affect the quality of weight loss

GLP-1-based medicines have transformed the treatment of both type 2 diabetes and obesity. One of the best-known active ingredients is semaglutide, which is found in medicines including Ozempic and Wegovy. Ozempic and Wegovy therefore contain the same active ingredient, but they are not used for exactly the same purpose. In the EU, Ozempic is approved for the treatment of type 2 diabetes, while Wegovy is approved for weight management in people with obesity and in certain cases of overweight.

Other medicines in the same area include liraglutide and the combined GIP/GLP-1 agonist tirzepatide. These medicines can lead to substantial weight loss. However, when body weight falls, it is not only body fat that is lost. Part of the weight loss may also consist of fat-free mass, often referred to as lean mass. For this reason, research has increasingly begun to focus on an important question: Not only how much weight is lost, but what type of body mass is lost.

Current research points in particular to two important measures for supporting muscle mass and physical function during substantial weight loss:

• adequate protein intake
• regular resistance training

Creatine has become an interesting area of research as a possible adjunct. The effects of creatine on muscle mass and strength are well studied in other populations, but direct clinical data in people using GLP-1 medicines are still limited.

What is Ozempic and how does GLP-1 work?

Ozempic contains semaglutide, a so-called GLP-1 receptor agonist. GLP-1 stands for glucagon-like peptide-1 and is a hormone involved, among other things, in the regulation of blood glucose, appetite and satiety. Semaglutide mimics some of the effects of the body’s natural GLP-1. This may contribute to:

• increased satiety
• reduced appetite
• lower energy intake
• improved blood glucose regulation

Ozempic is approved for the treatment of adults with type 2 diabetes. Wegovy also contains semaglutide, but is specifically approved for weight management in people who meet certain criteria for obesity or overweight.

Do you lose muscle when taking Ozempic, Wegovy and other GLP-1 medicines?

With substantial weight loss, the body does not normally lose fat tissue alone. Fat-free mass can also decrease. A systematic review and meta-analysis published in 2026 analysed 20 randomised controlled trials involving a total of 15,782 participants. The researchers compared changes in body composition during treatment with semaglutide, tirzepatide and liraglutide with various lifestyle interventions.

The proportion of total weight loss made up of lean mass was approximately:

The results also highlight an important point: loss of fat-free mass is not unique to Ozempic, Wegovy or other GLP-1 medicines. People who lose weight through lifestyle changes also typically lose a certain amount of fat-free mass. The most favourable changes in body composition, however, were seen when lifestyle intervention was combined with resistance training.

Lean mass is not the same as muscle mass

It is important not to automatically interpret lean mass as muscle. Lean mass, or fat-free mass, is a broader concept than skeletal muscle mass. When body composition is measured using methods such as DXA, lean mass includes:

• skeletal muscle
• body water
• organs
• connective tissue
• other fat-free tissues

This means that a result showing, for example, that 35 per cent of weight loss consisted of lean mass does not mean that 35 per cent of the body weight lost was muscle. It is therefore more relevant to also consider factors such as:

• muscle strength
• physical function
• skeletal muscle mass
• the ability to maintain physical activity

Why can Ozempic and other GLP-1 medicines make protein particularly important?

An important effect of GLP-1 medicines is that appetite decreases and satiety increases. For someone who previously ate large portions, food intake may therefore fall considerably. This is part of the mechanism behind weight loss, but it also means that the nutritional quality of the smaller amount of food becomes increasingly important. If energy intake falls significantly without careful dietary planning, intake of important nutrients may also decrease, including:

• protein
• essential fatty acids
• vitamins
• minerals

Nausea, early satiety or other gastrointestinal side effects can make it even more difficult for some people to eat enough food.

How much protein do you need when using GLP-1 medicines?

There is no universal amount of protein that is suitable for everyone using Ozempic, Wegovy or other GLP-1 medicines. During active weight loss, a relatively high protein intake is often discussed as a way of supporting muscle mass, particularly when combined with resistance training. Reference intakes of around 1.2–1.6 grams of protein per kilogram of body weight per day are frequently seen in the literature on weight loss and preservation of muscle mass. However, this does not mean that everyone should use their actual body weight for the calculation. For someone with a high body weight, this could result in a very high protein intake. In such cases, target weight, adjusted body weight or fat-free mass may be more appropriate. Protein requirements are also influenced by factors including:

• age
• muscle mass
• training level
• the rate of weight loss
• energy intake
• kidney function and other medical conditions

Protein is not enough – resistance training is just as important

Eating enough protein is important, but protein alone is not the whole solution. Muscles also need a signal that they are still required. That signal comes mainly from mechanical loading and resistance training. When someone loses a significant amount of weight, the natural load on the body also decreases. Someone who loses 20 kg, for example, no longer has to carry those extra 20 kg with every step, when standing up or when climbing stairs. This means that the natural workload placed on the muscles may decrease at the same time as the body is in an energy deficit. Resistance training may therefore be particularly important during periods of rapid weight loss. In the 2026 meta-analysis, the group that combined lifestyle intervention with resistance training had the lowest proportional loss of lean mass, at around 17.5 per cent of total weight loss.

Creatine and Ozempic – why have researchers become interested?

Creatine is a naturally occurring compound that is stored largely in skeletal muscle. In muscle, creatine forms part of the creatine-phosphocreatine system, which helps the body rapidly regenerate ATP – the energy used by muscles during short bursts of intense activity. This is an important reason why creatine has long been studied in connection with resistance training. The newer question is whether creatine may also be valuable for people using semaglutide, Ozempic, Wegovy, tirzepatide or other incretin-based medicines while undergoing substantial weight loss. There is a biologically plausible hypothesis: if creatine can support training capacity, strength and fat-free mass in other populations, it may also help improve the preservation of muscle during GLP-1-related weight loss. 

What do we already know about creatine and muscle mass?

Creatine is one of the most extensively studied supplements in the fields of exercise and muscle physiology. EFSA has previously assessed research on creatine and resistance training in people over the age of 55 and approved a health claim relating to improved muscle strength under specific conditions. This does not mean that the same effect can automatically be applied to people using GLP-1 medicines, but such an effect is certainly not implausible. 

Creatine and GLP-1 are now being studied in clinical research

The question has now moved from theory into clinical research. A randomised pilot study is investigating creatine supplementation in combination with resistance training in people starting treatment with GLP-1 receptor agonists. The study includes two groups, both of which follow a structured resistance-training programme.

Creatine group

• daily creatine supplementation
• resistance training three times per week
• 12-week intervention

Placebo group

• placebo
• the same resistance-training programme
• 12-week intervention

The researchers are examining changes in fat-free mass and physical function, among other outcomes. As the study is still ongoing, there are not yet any final results showing whether creatine actually helps preserve more muscle mass during GLP-1 treatment.

What is most important for preserving muscle when using Ozempic or other GLP-1 medicines?

Based on current research, there are several particularly important areas to focus on.

1. Do resistance training regularly

Resistance training sends a clear signal to the muscles that muscle tissue is still needed, even when the body is in an energy deficit.

2. Prioritise protein

As appetite decreases, the quality of the food you eat becomes more important. Protein should therefore play a central role in the diet.

3. Do not focus only on the number on the scales

Two people can lose exactly the same number of kilograms but experience completely different changes in body composition. High-quality weight loss is therefore not simply about maximising weight loss, but also about trying to preserve muscle mass, strength and physical function.

4. Stay physically active outside the gym as well

Resistance training is important, but everyday movement and general physical activity also help maintain physical function during weight loss.

5. Consider creatine an interesting potential adjunct 

Creatine has a substantial body of research supporting its use in resistance training and muscle performance, and research in this area is ongoing. It is entirely possible that future evidence will show that creatine can help counteract muscle loss associated with Ozempic, Wegovy or other GLP-1 medicines. 

Summary: the quality of weight loss is just as important as the number of kilograms lost

Medicines such as Ozempic have made GLP-1 a widely recognised term, while medicines such as Wegovy have been specifically developed and approved for weight management. Both contain semaglutide, but their approved uses differ. When semaglutide, tirzepatide and other incretin-based medicines lead to substantial weight loss, the question of body composition becomes increasingly important. Part of the weight lost may consist of fat-free mass, but the same phenomenon also occurs during conventional weight loss. Research points in particular to three key areas:

1. resistance training + 2. adequate protein + 3. a nutrient-dense diet: Creatine is an interesting potential adjunct because there is already a substantial body of research on creatine, muscle strength and resistance training in other populations. However, research still needs to answer one specific question: Can creatine help people using Ozempic, Wegovy or other GLP-1 medicines preserve more muscle mass and physical function during weight loss? We do not yet know. Ongoing clinical research will hopefully provide a clearer answer.