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Does semaglutide make you lose muscle instead of fat?

Robbie Puddick
Written by

Robbie Puddick

Medically reviewed by

Fiona Moncrieff

6 min read
Last updated June 2024

Jump to: Not all lean mass is created equal | So, does semaglutide destroy muscle? | How do you prevent muscle loss on semaglutide? | Take home message

According to data from two randomised controlled trials (STEP 1 and SUSTAIN 8), up to 40% of the weight lost on semaglutide (Wegovy/Ozempic) may be from lean mass.

This perceived high level of lean mass loss has led some health experts to criticise the use of these medications and suggest that the weight patients lose on these medications ‘isn’t healthy’.

However, looking at this percentage in isolation oversimplifies the complexities of weight loss and the body’s transition during this process.

Firstly, while STEP 1 and SUSTAIN 8 reported high levels of total lean mass loss on semaglutide, the average proportion of lean mass to total body weight in the participants actually increased after they lost weight.

For example, in the STEP 1 trial, the total proportion of lean mass in the participants at baseline was 53.9%. (Simply put, their muscles, bones, and other lean tissues accounted for 53.9% of their body weight.)

At the end of the trial, after they had lost 15% of their body weight, their total lean mass increased by three percentage points and accounted for nearly 57% of their total body weight.

Wegovy (semaglutide) Muscle Loss

So, because these participants had a high weight at baseline, they also accrued lean mass over the years of being overweight. Losing some lean mass alongside fat when losing this much total weight is expected.

Additionally, much of the lean mass lost during weight loss might not come directly from lean tissues like bone and muscle.

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Semaglutide muscle loss? Not all lean mass is created equal

When discussing lean mass, many people associate it with bone, muscle, and organs like our skin. However, many tissues in the body would be considered ‘lean’ because they’re not fat tissue.

For example, our fat tissue (our adipose tissue) comprises stored fat cells and other non-fat lean tissues like water.

Research has shown that most (if not all) of the lean tissue lost during weight loss may be non-fat lean tissues (like water) found in our fat cells (adipose tissue).

One study compared the impact of three different exercise and diet interventions on weight loss and lean mass.

The study showed that all three groups lost an average weight loss of 9kg, and their lean mass decreased by 2.7kg.

However, when the researchers accounted for the amount of lean tissue lost from adipose tissue, they found that the participants increased their total lean mass from other tissues by 0.3kg.

This effect has been replicated by other researchers who found a similar relationship between the loss of non-fat lean tissue from our adipose tissue during weight loss.

To circle back to the effect of semaglutide on lean mass loss. Neither STEP 1 nor SUSTAIN 8 trials analysed the amount of non-fat lean tissue lost from the participant’s adipose tissue.

So, it’s possible that a large proportion of the lean tissue loss reported in the studies was from non-fat lean tissues (like water) in our adipose tissue.

So, does semaglutide destroy muscle?

Based on the observation that a large proportion of lean tissues lost during weight loss seems to be from our adipose tissue, and the proportion of total lean mass increased after weight loss in STEP 1 and SUSTAIN 8 trials, it’s unlikely that using semaglutide to support weight loss leads to clinically meaningful reductions in muscle and other lean tissues.

Additionally, recent research on patients taking oral semaglutide (Rybelsus) to help manage type 2 diabetes has shown that losing lean mass during weight loss with semaglutide isn’t always a certainty.

A study published in 2023 investigated the effect of oral semaglutide (Rybelsus) on blood sugar, weight, and lean mass in 25 participants.

The results showed that the participants significantly reduced their BMI by 4.3% and lost 2.8kg of body fat after 24 weeks. However, their lean mass levels didn’t change.

This might be attributed to the attention the study paid to providing adequate diet and exercise advice to the participants. To quote the study:

‘The attending doctors asked the patients about changes in eating and exercise in every visit, and all patients answered to continue diet and exercise therapy with [the] same level according to advice and instructions from the attending doctors and medical staff.’

By paying close attention to the quality of our diet and exercising enough, we can prevent potential losses of lean mass during weight loss with semaglutide.

How do you prevent muscle loss on semaglutide?

You can prevent muscle loss on semaglutide (Wegovy/Ozempic) by eating enough calories and protein, performing strength training 1-2 times a week, and aiming for 7-9 hours of sleep a night.

You can read our article on how to lose fat without losing muscle if you want an in-depth review of this topic.

However, here’s a quick summary of how to lose fat without losing muscle on semaglutide:

1) Eat enough protein: The amount of protein you eat is critical to successful weight loss. Aim for 20-40 grams of protein in each of your main meals; this includes breakfast. Great sources include yoghurt, other dairy products, eggs, meat, fish, seafood, tofu, and tempeh.

2) Resistance (strength) training: If you want to try and join a gym, great, but you don’t need to and can get all the benefits of strength training from the comfort of your home. Try to snack on exercise throughout the day to kickstart your resistance training habit by doing push-ups while the kettle boils and squats whilst you cook.

3) Make sure you eat enough: Crash diets lead to a starvation response by your brain, which may see your body breaking down lean tissue to provide an energy source as it tries to protect your fat stores. A calorie deficit of around 10% and eating a diet based on whole foods can help you lose weight sustainably without losing excess lean tissue.

4) Get enough sleep: Aim for 7-9 hours a night. Have a regular sleep schedule, avoid caffeine after midday, and screen 30 minutes before bedtime.

Take home message

In this article, we’ve provided evidence that semaglutide doesn’t necessarily lead to a significant loss of lean body mass during weight loss.

However, this isn’t to say that losing muscle and lean tissues while losing weight on semaglutide isn’t a possibility.

It’s possible to lose muscle and lean tissue during any weight loss journey if we’re not approaching it in the right way. Be sure to consider our suggestions above on how to lose fat without losing muscle.

But, if you’re currently on semaglutide or considering semaglutide to support your weight loss journey, feel reassured that it’s unlikely to adversely affect your muscle and lean tissues if you approach weight loss in the right way.

Not a magic pill

Weight-loss injections are designed as additional tools for healthy lifestyle change and shouldn’t be considered as lifelong medications.

Instead, they should be used to help you kickstart your weight-loss journey whilst you focus on building new, healthy habits.

Consider the use of antidepressants for people living with depression. They’re not designed to cure the condition. Instead, they’re designed to allow room for therapy to treat the condition’s underlying cause.

Mounjaro and Wegovy are similar. These medications can help silence food-related thoughts and also give you a boost of confidence with more immediate weight-loss results.

This helps to buy you the time and headspace to understand why your body may have struggled to lose weight previously, and to build new long-term healthy habits.

The core focus of our medication programmes are to calm down the feeling of food noise, lower your cravings, and to allow you to build healthier habits to keep the weight off for good.

The ultimate goal is to make losing weight feel second nature.

Second Nature’s medication-supported programmes

Second Nature has two medication-supported programmes: a Wegovy weight-loss programme and a Mounjaro weight-loss programme.

If you’ve made the decision to try Wegovy or Mounjaro (assuming you’re eligible), why should you choose Second Nature over other medication providers?

For peace of mind.

Second Nature has worked with the NHS for over 6 years providing weight-loss programmes across the UK.

Whilst our Wegovy and Mounjaro weight-loss programmes are private and not currently used by the NHS, we’ve built the programmes with a focus on scientific evidence, patient safety, and data security.

We hope that our 6+ years of working with the NHS and building a track record of effective weight-loss results will give you peace of mind to give us a try.

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