Gram Research analysis of the STEP UP trial shows that semaglutide reduces body fat by 11.1 liters and improves muscle quality by decreasing fat within muscles by 0.92 percentage points. However, people also lost approximately 1.1 liters of thigh muscle volume while taking the medication. The important finding: despite losing some muscle tissue, participants maintained their physical strength and ability to perform daily activities like standing up and sitting down, with no decline in functional performance over 72 weeks.
A major study of semaglutide, a popular weight loss medication, found that the drug helps people shed significant amounts of body fat when combined with lifestyle changes. However, researchers discovered that people also lost some muscle tissue along with the fat. The good news: muscle strength and the ability to stand up and sit down repeatedly stayed about the same. This secondary analysis of the STEP UP trial examined detailed body scans from 55 participants to understand exactly what happens to muscle and fat when people take this medication for 72 weeks.
Key Statistics
A secondary analysis of the STEP UP trial involving 55 participants found that semaglutide reduced total body fat by 11.1 liters compared to placebo over 72 weeks.
According to research reviewed by Gram, semaglutide decreased fat infiltration within thigh muscles by 0.92 percentage points, indicating improved muscle quality despite some muscle volume loss.
The 2026 STEP UP analysis showed that people taking semaglutide lost approximately 1.1 liters of thigh skeletal muscle volume, yet maintained stable sit-to-stand performance at 13 to 15 repetitions in 30 seconds.
Semaglutide reduced visceral fat (dangerous fat around organs) by 1.5 liters in the 72-week STEP UP trial, a significant reduction in metabolic risk factors.
The Quick Take
- What they studied: How semaglutide affects the amount and quality of muscle tissue and fat in people with obesity, and whether physical strength is preserved during weight loss.
- Who participated: Adults with obesity (body mass index of 30 or higher) from the STEP UP trial. This specific analysis included 55 people who had detailed MRI scans: 49 received semaglutide and 6 received placebo over 72 weeks.
- Key finding: Semaglutide reduced total body fat by 11.1 liters and reduced fat inside muscles by 0.92 percentage points compared to placebo. However, people also lost about 1.1 liters of thigh muscle volume. Despite this, their ability to stand up and sit down repeatedly remained stable at about 13 to 15 repetitions in 30 seconds.
- What it means for you: If you take semaglutide for weight loss, you’ll likely lose significant fat, which is beneficial. Some muscle loss may occur, but your functional strength for everyday activities appears to be maintained. Combining the medication with exercise and healthy eating may help preserve muscle better, though more research is needed.
The Research Details
This was a secondary analysis of the STEP UP trial, a large phase 3b clinical trial that tested semaglutide in adults with obesity. Researchers randomly assigned 1,407 people to receive either semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo once per week as injections for 72 weeks. All participants also received lifestyle counseling about diet and exercise.
For this specific analysis, researchers focused on 55 participants who had detailed MRI scans (a type of medical imaging that shows muscle and fat in great detail) at the beginning and end of the study. They measured the exact volume of fat tissue, visceral fat (fat around organs), lean tissue, and thigh muscle. They also tested how many times people could stand up and sit down in 30 seconds, which measures leg strength and function.
The researchers compared changes in muscle and fat between the semaglutide group and the placebo group to see what effect the medication had beyond just weight loss.
Understanding what happens to muscle tissue during weight loss is crucial because losing muscle can make people weaker and less able to do daily activities. This study used advanced imaging to see exactly what’s happening inside the body, rather than just measuring weight on a scale. This detailed approach helps doctors understand whether weight loss medications are safe for long-term use and whether people should combine them with exercise to protect their muscles.
This study has some important limitations. The sample size for the detailed imaging analysis was very small (only 55 people), which makes it harder to be confident in the results. The study was only 72 weeks long, so we don’t know what happens over years of use. The researchers did use high-quality MRI imaging to measure muscle and fat precisely, which is a strength. The study was randomized and controlled, meaning people were randomly assigned to groups, which helps reduce bias.
What the Results Show
Semaglutide combined with lifestyle changes significantly reduced body fat. People taking semaglutide lost an average of 11.1 liters of total body fat compared to the placebo group. They also lost 1.5 liters of visceral fat, which is the dangerous fat that surrounds organs and increases disease risk.
The medication also improved the quality of remaining muscle tissue. Fat infiltration in thigh muscles (meaning fat deposits within the muscle itself) decreased by 0.92 percentage points in the semaglutide group compared to placebo. This is actually good news because it means the muscle tissue that remains is healthier and less fatty.
However, people taking semaglutide did lose some muscle volume. Thigh skeletal muscle volume decreased by about 1.1 liters compared to placebo. This represents a loss of muscle tissue along with the fat loss.
Despite losing muscle volume, people’s physical function remained stable. Both groups could perform about 13 to 15 sit-to-stand repetitions in 30 seconds at baseline and at the end of the study, showing that leg strength and functional ability were preserved.
The study found similar results when researchers analyzed just the highest dose of semaglutide (7.2 mg) compared to placebo. Lean body tissue (all non-fat tissue including muscle, bone, and organs) decreased by 1.7 liters in the semaglutide group, though this difference was not statistically significant. The relative changes in muscle and fat percentages showed similar patterns to the absolute volume changes.
Previous research on weight loss has shown that people typically lose both fat and muscle when they lose weight, especially without exercise. This study confirms that pattern with semaglutide. However, the finding that muscle fat infiltration improved is encouraging and suggests the medication may improve muscle quality even as volume decreases. Other weight loss studies have shown similar muscle loss, but few have examined muscle quality in detail like this study did.
The biggest limitation is the very small sample size for the imaging analysis: only 55 people had detailed scans, with just 6 in the placebo group. This makes it difficult to be confident in the results. The study lasted only 72 weeks, so we don’t know if muscle loss continues or stabilizes over longer periods. The study didn’t measure whether participants exercised, so we can’t tell if exercise would have prevented muscle loss. Additionally, the study focused only on thigh muscle, not total body muscle, so we don’t know if other muscles were affected differently.
The Bottom Line
If you’re considering semaglutide for weight loss, understand that you’ll likely lose both fat and some muscle tissue. To minimize muscle loss, combine the medication with regular strength training and adequate protein intake. Moderate to high confidence: the fat loss benefits appear substantial and the muscle loss may be acceptable given the overall health improvements. Low to moderate confidence: exercise may help preserve muscle, but this study didn’t directly test that.
This research is most relevant for adults with obesity considering semaglutide treatment. It’s particularly important for older adults and people concerned about maintaining strength and mobility. People with existing muscle weakness or mobility problems should discuss these findings with their doctor. This research is less relevant for people at healthy weights or those with different types of obesity-related conditions.
The changes measured in this study occurred over 72 weeks (about 1.5 years). Most fat loss typically happens in the first 6 months of treatment. Muscle loss appears to happen gradually alongside fat loss. You might notice improved physical function within weeks as you lose weight, even if muscle volume decreases slightly. Long-term effects beyond 72 weeks are unknown.
Frequently Asked Questions
Does semaglutide cause muscle loss when you lose weight?
Yes, the STEP UP trial found that semaglutide users lost about 1.1 liters of thigh muscle volume over 72 weeks. However, their functional strength remained stable, and muscle quality improved because fat deposits within muscles decreased.
Will I be weaker if I take semaglutide for weight loss?
The research suggests your functional strength should remain stable. Participants maintained their ability to perform sit-to-stand repetitions despite losing muscle volume, indicating that everyday strength for activities like climbing stairs or getting out of chairs is preserved.
How much fat does semaglutide actually remove from your body?
In the STEP UP trial, semaglutide reduced total body fat by 11.1 liters and visceral fat by 1.5 liters over 72 weeks compared to placebo. This represents a substantial reduction in both overall fat and dangerous fat around organs.
Can I prevent muscle loss while taking semaglutide?
This study didn’t directly test exercise, but combining semaglutide with strength training and adequate protein intake (25 to 30 grams per meal) is likely to help preserve muscle. More research is needed to confirm the best approach.
Is the muscle loss from semaglutide permanent?
The study only measured changes over 72 weeks, so long-term effects are unknown. Muscle tissue can be rebuilt through strength training and adequate protein, so the loss may not be permanent if you exercise after weight loss.
Want to Apply This Research?
- Track weekly sit-to-stand repetitions (how many times you can stand up and sit down in 30 seconds) as a measure of leg strength. This is the exact test used in the research and provides an objective measure of functional strength independent of weight loss.
- Add 2 to 3 strength training sessions per week focusing on leg exercises like squats, lunges, and step-ups. Log these sessions in your app along with protein intake at each meal (aim for 25 to 30 grams per meal) to support muscle preservation during weight loss.
- Monthly: measure sit-to-stand repetitions and track average daily protein intake. Quarterly: take progress photos and note changes in how clothes fit and energy levels. This multi-metric approach captures both the muscle loss shown in research and the functional strength that was preserved.
This research is a secondary analysis of a clinical trial and should not replace medical advice from your healthcare provider. The study involved a small sample size for imaging analysis (55 participants) and lasted only 72 weeks, so results may not apply to all people or longer time periods. If you’re considering semaglutide or any weight loss medication, consult with your doctor about potential benefits and risks, especially regarding muscle preservation. This article is for educational purposes and does not constitute medical advice.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.