GLP-1 & Muscle Loss: Do Semaglutide or Tirzepatide Cause Muscle Wasting?
- Joshua Silva, MD
- Nov 7, 2025
- 13 min read
Updated: Jan 20
Medically authored by Joshua Silva, MD | Evidence-Based Weight Loss at Potere Health MD
As GLP-1 and GLP-1/GIP medications such as semaglutide (Wegovy®, Ozempic®) and tirzepatide (Zepbound®, Mounjaro®) continue to transform medical weight management, one question comes up repeatedly:
Do these medications cause muscle loss—or even muscle wasting?
Quick answer
No. Semaglutide and tirzepatide do not directly cause muscle wasting. Some lean-mass reduction can occur during meaningful weight loss, but clinical trials consistently show that most weight lost is fat, not muscle. With adequate protein intake and resistance training, muscle loss can be minimized and functional strength preserved.⁴ ⁹ ¹¹
At Potere Health MD, our physician-supervised medical weight-loss programs are designed to reduce fat while actively preserving muscle through evidence-based nutrition and strength guidance.
Key takeaways
GLP-1 medications do not inherently cause muscle wasting.⁴ ⁹
Most weight lost on semaglutide or tirzepatide is fat, not muscle.⁴ ⁹
Some lean-mass loss during weight loss reflects adaptive remodeling, not pathology.²
Adequate protein intake and resistance training significantly reduce muscle loss during GLP-1 therapy.³ ⁵
Do GLP-1 Medications Cause Muscle Wasting?
Answer: No. GLP-1 receptor agonists (semaglutide) and dual GLP-1/GIP receptor agonists (tirzepatide) do not directly cause muscle wasting. Clinical trial data using body-composition analysis show that fat mass accounts for the majority of weight loss, while lean-mass changes reflect normal physiologic adaptation to reduced body weight and energy intake.⁴ ⁹
Understanding this distinction is critical—because muscle wasting and expected lean-mass adaptation are not the same thing.
What Is Muscle Wasting?
Muscle wasting refers to pathologic loss of muscle tissue caused by illness, prolonged undernutrition, immobilization, or systemic disease. It differs from the modest lean-mass reduction seen during weight loss, where the body adapts to lower energy needs. During GLP-1–associated weight loss, lean-mass changes are typically adaptive and preventable, not degenerative.² ³
GLP-1 Body Composition Changes: What Clinical Trials Show About Muscle Loss
Clinical trials and body-composition sub-studies of semaglutide and tirzepatide consistently demonstrate:
Fat mass accounts for most weight lost during treatment.⁴ ⁹
Lean mass may decrease, particularly without resistance training or adequate protein intake.⁴ ⁹
In many patients, the proportion of lean mass relative to total body weight is preserved or improved, because fat loss exceeds lean loss.⁴
Key clinical insight: GLP-1/GIP therapies improve overall body composition by preferentially reducing fat mass—not by causing muscle breakdown.⁴ ⁹
Lean mass refers to all the non-fat tissues in the body—primarily skeletal muscle, but also organs, bones, connective tissue, and body water—that support metabolism, movement, and overall physical function.
Why GLP-1–Related Muscle Loss Is Adaptive Remodeling — Not Muscle Wasting
All effective weight-loss interventions—dietary, surgical, exercise-based, or pharmacologic—reduce both fat and lean tissue to some degree. This reflects adaptive remodeling, not disease.
Energy economics of muscle and fat during weight loss
Different tissues have different metabolic demands. Skeletal muscle is metabolically active and costly to maintain, while adipose tissue stores energy more efficiently. When calorie intake declines, the body adapts by lowering total energy requirements, which can include modest reductions in lean tissue.¹
Mechanical load and mechanotransduction
Skeletal muscle depends on mechanical stress to maintain size and strength—a process governed by mechanotransduction.²
Example: If a person weighs 250 lb, their muscles perform constant load-bearing work. After losing 50 lb, that mechanical demand drops substantially. Without intentional resistance training, the body appropriately reduces muscle mass to match the new workload.
This is the same physiologic process seen when someone stops lifting weights: muscle size decreases because the stimulus is gone—not because muscle is being “destroyed.”²
Common Misconception: “GLP-1 Drugs Burn Muscle”
Reality: Muscle loss during GLP-1–associated weight loss is driven by reduced mechanical load and insufficient protein/calories, not by a toxic or catabolic drug effect.² ⁴ ⁹
When Lean-Mass Loss Becomes True Muscle Wasting
True muscle wasting is uncommon with GLP-1 therapy and is usually related to undernutrition, not the medication itself.
Risk increases with:
Too few calories or skipped meals, leading to protein breakdown for energy
Inadequate protein intake, especially near minimal dietary requirements rather than weight-loss–appropriate targets³ ⁶
Lack of resistance training, removing the signal to maintain muscle² ⁵
Micronutrient deficiencies, such as low vitamin D, which can impair muscle function⁸
Preventing undernutrition dramatically reduces the risk of clinically meaningful muscle loss.³ ⁵ ⁶
How Common Is Lean-Mass Loss with GLP-1/GIP Therapy?
Across major trials:
Lean mass typically represents 25–40% of total weight lost, meaning 60–75% is fat loss.⁴ ⁹
Imaging studies suggest tirzepatide may improve muscle quality, reducing fat infiltration within muscle tissue—even as total lean mass declines.¹⁰
A prospective 12-month semaglutide study demonstrated favorable body-composition changes with preserved or improved functional outcomes in some participants.¹¹
In short: body composition improves, even when the scale shows lean-mass reduction.⁴ ⁹ ¹⁰ ¹¹
Muscle Changes by Weight-Loss Method
Weight-loss method | Muscle loss expected? | Primary driver |
Calorie restriction without resistance training or adequate protein | Moderate–high | Energy deficit with inadequate mechanical loading and protein availability |
GLP-1 mediated weight loss without resistance training | Moderate | Energy deficit from reduced intake with decreased mechanical load |
GLP-1 + protein + resistance training | Minimal | Preserved muscle protein synthesis via nutrition and mechanical signaling |
Illness or malnutrition | High | Catabolic state driven by inflammation, hormonal stress, and undernutrition |
How to Preserve Muscle on Semaglutide or Tirzepatide
Protein targets for GLP-1 patients
A clinically supported target for preserving lean mass during weight loss is:
1.2–1.6 g/kg/day (≈ 0.54–0.73 g/lb/day) for most adults³ ⁶
Higher intakes —approximately 0.7–1.0 g per pound of body weight per day—may be beneficial for individuals performing regular resistance training, particularly during calorie restriction, to better preserve or increase lean mass.⁵ ⁷
Distributing protein across meals (often ~25–40 g per meal) supports muscle protein synthesis.³ ⁷
Resistance training 2–3× per week
Resistance training provides the mechanical signal required to retain muscle.².
Protein supplementation combined with resistance training leads to greater preservation of lean mass and strength than training alone.⁵
Key point: With adequate protein intake and resistance training, patients can maintain—and sometimes increase—strength during GLP-1 therapy despite overall weight loss.⁵
Recovery and micronutrients
Adequate sleep, hydration, and correction of deficiencies (including vitamin D when present) further support muscle function and recovery.⁸
Bottom Line: GLP-1 Medications Improve Body Composition — Not Muscle Wasting
Semaglutide and tirzepatide do not inherently cause muscle wasting.⁴ ⁹
Most weight lost is fat, and body composition improves.⁴ ⁹
Muscle wasting is primarily a risk of undernutrition, not GLP-1 therapy itself.³ ⁵ ⁶
Protein + resistance training is the most effective strategy to preserve muscle.² ³ ⁵ ⁶
At Potere Health MD, GLP-1 and GIP therapy is paired with evidence-based nutrition and strength guidance so weight loss is healthier, stronger, and more sustainable.
Disclaimer
This article is for educational purposes only and is not a substitute for medical advice.
About the Author
Dr. Joshua Silva, MD, is a licensed physician and Medical Director of Potere Health MD. He earned his medical degree from the University of Hawaiʻi John A. Burns School of Medicine and completed residency training in Occupational and Environmental Medicine at the University of Utah, where he also earned a master’s degree in Occupational Health. He later completed a Master of Business Administration with an emphasis in health care administration at Ohio University.
Dr. Silva specializes in evidence-based weight management, including GLP-1 and GIP therapies such as semaglutide and tirzepatide. He provides in-person and virtual care for patients in Salt Lake City, St. George, and Cedar City, Utah.
Sources:
1. Metabolic Rate of Different Tissues
Wang Z et al. Specific metabolic rates of major organs and tissues across adulthood. Am J Clin Nutr. 2010; 92(6):1369-1377. doi:10.3945/ajcn.2010.29885.
2. How Mechanical Stress Builds Muscle
Mirzoev TM. Mechanotransduction for Muscle Protein Synthesis via Mechanically Activated Ion Channels. Life (Basel). 2023; 13(2):341. doi:10.3390/life13020341.
3. Protein Intake and Muscle Preservation
Nunes EA et al. Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults. J Cachexia Sarcopenia Muscle. 2022; 13(2):795-810. doi:10.1002/jcsm.12922.
4. Body-Composition Effects of Semaglutide (STEP 1 Study)
Wilding JPH et al. Impact of Semaglutide on Body Composition in Adults With Overweight or Obesity: Exploratory Analysis of the STEP 1 Study. J Endocr Soc. 2021; 5(Suppl 1):A16–A17. doi:10.1210/jendso/bvab048.030.
5. Protein & Resistance Training Meta-Analysis
Morton RW et al. A systematic review and meta-analysis of protein supplementation on resistance-training-induced gains in muscle mass and strength. Br J Sports Med. 2018; 52(6):376-384. doi:10.1136/bjsports-2017-097608.
Read on PubMed ›
6. High-Protein Diets and Muscle Retention During Weight Loss
Pasiakos SM et al. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 2013; 27(9):3837-47. doi:10.1096/fj.13-230227.
7. Sports-Nutrition Guidelines (ACSM Position Stand)Thomas DT, Erdman KA, Burke LM. Position of the Academy of Nutrition and Dietetics, Dietitians of Canada, and the American College of Sports Medicine: Nutrition and Athletic Performance. J Acad Nutr Diet. 2016; 116(3):501-528. doi:10.1016/j.jand.2015.12.006.
8. Vitamin D and Muscle FunctionBeaudart C et al. The Effects of Vitamin D on Skeletal Muscle Strength, Mass, and Power: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. 2014; 99(11):4336-4345. doi:10.1210/jc.2014-1742.
9. Body-Composition Effects of Tirzepatide (SURMOUNT-1 Study)
Look M, Dunn JP, Kushner RF, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab. 2025; (ePub ahead of print). doi:10.1111/dom.16039.
10. Tirzepatide and Muscle Composition (MRI Analysis)
Tirzepatide and muscle composition changes in people with type 2 diabetes. Lancet Diabetes Endocrinol. 2025; (ePub ahead of print). doi:10.1016/S2213-8587(25)00027-0.
11. Semaglutide and Body Composition (12-Month Prospective Study)
van Baak MA, Brakema EA, Wijngaarden M van der, et al. Body composition and metabolic changes following 12 months of semaglutide 2.4 mg in adults with obesity: a prospective study. Diabetes Obesity and Metabolism. 2025; (ePub ahead of print).
Answer: Not directly. Some lean mass reduction occurs during any meaningful weight loss — but this is better understood as adaptive body remodeling, not “muscle wasting.” Let’s unpack what the science shows.
At Potere Health MD, serving St George, Cedar City, and Salt Lake City Utah, our physician-supervised programs are grounded in clinically backed evidence, not social media trends or influencer opinions. Every recommendation for preserving lean muscle is guided by science, safety, and your individual health goals.
GLP-1 Body Composition Changes — What Trials Show About Lean Mass
Clinical trials of semaglutide and tirzepatide consistently demonstrate that effective GLP-1 weight loss reduces both fat and lean mass, with fat making up the majority of the loss (DXA substudies). This pattern reflects normal, adaptive remodeling rather than pathologic muscle breakdown.
STEP (semaglutide) Clinical Trial: Most loss from fat mass; the percentage of lean mass often increases.
SURMOUNT-1 (tirzepatide) Clinical Trial: Fat-mass loss predominates across subgroups.
Key takeaway for GLP-1 therapy and muscle: the body rebalances tissues as weight and energy needs decline.
Why It’s “Adaptive Remodeling,” Not Muscle Wasting
Every effective weight-loss intervention — diet, exercise, surgery, or medication — causes the body to lose both fat and lean tissue. This is not muscle “wasting” but part of a normal, adaptive remodeling process that restores balance between energy storage and energy use.
Energy Economics During GLP-1 Weight Loss
Muscle tissue is metabolically expensive to maintain. At rest, muscle burns roughly 6 kcal per pound per day, while fat burns about 2 kcal per pound per day.
Fat also serves as the body’s stored fuel reserve. One pound of fat contains about 3,500 kcal of energy, whereas one pound of muscle tissue yields roughly 350 kcal when adjusted for water and non-energy components.
When calorie intake declines — whether through semaglutide, tirzepatide, or other means — the body prioritizes energy conservation. It does this by scaling back tissue that is no longer needed or heavily used. In evolutionary terms, fat storage offers survival value, while excess muscle increases energy expenditure.
To conserve energy, the body trims unneeded muscle and preserves energy-dense fat. This is why, without ongoing resistance training or other forms of mechanical load, muscle that once served to support higher body weight will naturally diminish when that weight — and its mechanical demand — are gone.
Mechanical Load and GLP-1 Exercise
Skeletal muscle depends on mechanical stress for its growth and maintenance — a principle known as mechanotransduction.
If you weigh 250 lb, every step acts as a form of resistance training, and your muscles adapt by growing stronger to support that extra load. When you lose 50 lb, there is a proportional decrease in mechanical stress on those muscles. The body appropriately scales back muscle mass to meet the new, less demanding task of supporting 200 lb.
This adjustment is not a sign of pathological muscle loss. It’s the same process that occurs when a bodybuilder stops lifting — the muscle simply shrinks to match the reduced workload. In both cases, the body is returning to equilibrium, not wasting away.
Evolutionary Logic
From an evolutionary perspective, fat serves as stored fuel, while muscle functions as energy-consuming infrastructure. During times of energy scarcity (dieting), conserving fuel and minimizing maintenance costs is a survival advantage.
The body therefore tends to preserve fat stores while trimming unneeded muscle mass—unless regular exercise signals that muscle remains necessary and adequate protein intake supports its maintenance.
When GLP-1 Muscle Loss Can Become Muscle Wasting — Malnutrition Risks
While moderate lean-mass reduction during weight loss is a normal adaptive process, true muscle wasting can occur if the body becomes undernourished. This risk applies to any weight-loss method — whether diet-based or medication-assisted.
Too few calories: Severe caloric restriction or skipping meals forces the body to break down muscle protein for energy, especially when overall intake drops below basal needs.
Too little protein: Inadequate protein intake (<0.8 g/kg/day) accelerates muscle breakdown, while 1.2–1.6 g/kg/day helps preserve lean tissue. Appetite suppression from GLP-1 or GLP-1/GIP therapy can make this deficiency more likely without intentional meal planning.
Micronutrient gaps: Deficiencies in vitamin D, magnesium, or B-vitamins further impair muscle maintenance.
GLP-1 & tirzepatide bottom line: Prevent malnutrition, and muscle wasting is unlikely.
How Common Is Muscle Loss with GLP-1/GIP Therapy?
Across major GLP-1/GIP clinical trials:
Lean mass accounts for about 25–40% of total weight lost — meaning roughly 60–75% is fat loss.
The majority of weight reduction is fat, increasing the proportion of lean tissue after treatment.
Emerging imaging studies suggest tirzepatide may improve muscle quality, reducing fat infiltration within muscle tissue even as overall lean mass decreases—indicating a potential improvement in muscle composition rather than functional loss.
Similarly, a recent semaglutide study demonstrated improved muscle composition and functionality, with hand-grip strength increasing by approximately 4 kg over 12 months — evidence that muscle tone and performance can improve even as body weight declines.
Exercise and adequate protein help patients preserve more muscle on semaglutide or tirzepatide.
In short: GLP-1/GIP therapies improve body composition, helping you lose fat while maintaining — and often improving — your lean-mass ratio and muscle function.
How to Preserve Muscle on Semaglutide or Tirzepatide
Protein Targets for GLP-1 Patients
Target protein intake: 1.2–1.6 g/kg/day (≈0.54–0.73 g/lb/day) to preserve lean mass during GLP-1/GIP weight loss. This range supports muscle maintenance and recovery while calories are reduced.
For individuals performing regular resistance or strength training, higher protein intakes of 1.6–2.2 g/kg/day (≈ 0.7–1.0 g/lb/day) may further enhance muscle growth, repair, and recovery, particularly when total calories are reduced.
Sample day (~110 g for a 180-lb person):
Breakfast: Greek yogurt + berries + nuts (≈25 g)
Lunch: Chicken or tofu + beans salad (≈30–35 g)
Snack: Whey shake or cottage cheese (≈20 g)
Dinner: Salmon + quinoa + veggies (≈30–35 g)
Pro tip for GLP-1 nutrition: Distribute ≈25–40 g protein per meal to optimize muscle protein synthesis.
Resistance Training 2–3x/Week
Strength or body-weight training (squats, hinges, pushes, pulls, bands) provides the mechanical signal to retain muscle during GLP-1 therapy. Start light, focus on compound moves, and progress gradually.
Recovery & Micronutrients
Support muscle maintenance with adequate sleep, hydration, and correction of vitamin D/magnesium deficiencies when present.
Bottom Line on GLP-1, Tirzepatide, and Muscle
Semaglutide and tirzepatide do not inherently cause muscle wasting.
True muscle wasting can occur during any form of weight loss if caloric intake, protein, or essential micronutrients are inadequate.
Most weight lost with GLP-1/GIP therapy is fat, and overall body composition improves.
Emerging imaging studies suggest tirzepatide may improve muscle quality, reducing fat infiltration within muscle tissue even as overall lean mass decreases—indicating a potential improvement in muscle composition rather than functional loss.
Hitting protein targets of 1.2–1.6 g/kg/day (≈ 0.54–0.73 g/lb/day) and performing resistance training 2–3× per week helps preserve and even build lean mass.
In short: healthy weight loss requires sufficient calories, adequate protein, and mechanical stimulus. GLP-1 and GLP-1/GIP therapies work best when paired with proper nutrition and purposeful movement.
At Potere Health MD, every aspect of your weight-loss care—education, guidance, and decision-making—is grounded in clinical research, not marketing trends. We help patients across St George, Cedar City, and Salt Lake City Utah achieve healthy, sustainable weight control through physician-supervised GLP-1 and GIP programs that emphasize evidence, safety, and lasting results.
Disclaimer:
This article is for educational purposes only and is not a substitute for medical advice.
About the Author
Dr. Joshua Silva, MD, is a licensed physician and Medical Director of Potere Health MD. After graduating medical school from the University of Hawaii, he completed residency training in Occupational and Environmental Medicine from the University of Utah where he also earned a master's degree in Occupation Health. He now specializes in evidence-based weight management, including GLP-1/GIP therapies (semaglutide & tirzepatide). Dr. Silva provides in-person and virtual care for patients with clinics in Salt Lake City, St. George, and Cedar City, Utah.
Sources:
1. Metabolic Rate of Different Tissues
Wang Z et al. Specific metabolic rates of major organs and tissues across adulthood. Am J Clin Nutr. 2010; 92(6):1369-1377. doi:10.3945/ajcn.2010.29885.
2. How Mechanical Stress Builds Muscle
Mirzoev TM. Mechanotransduction for Muscle Protein Synthesis via Mechanically Activated Ion Channels. Life (Basel). 2023; 13(2):341. doi:10.3390/life13020341.
3. Protein Intake and Muscle Preservation
Nunes EA et al. Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults. J Cachexia Sarcopenia Muscle. 2022; 13(2):795-810. doi:10.1002/jcsm.12922.
4. Body-Composition Effects of Semaglutide (STEP 1 Study)
Wilding JPH et al. Impact of Semaglutide on Body Composition in Adults With Overweight or Obesity: Exploratory Analysis of the STEP 1 Study. J Endocr Soc. 2021; 5(Suppl 1):A16–A17. doi:10.1210/jendso/bvab048.030.
5. Protein & Resistance Training Meta-Analysis
Morton RW et al. A systematic review and meta-analysis of protein supplementation on resistance-training-induced gains in muscle mass and strength. Br J Sports Med. 2018; 52(6):376-384. doi:10.1136/bjsports-2017-097608.
Read on PubMed ›
6. High-Protein Diets and Muscle Retention During Weight Loss
Pasiakos SM et al. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 2013; 27(9):3837-47. doi:10.1096/fj.13-230227.
7. Sports-Nutrition Guidelines (ACSM Position Stand)Thomas DT, Erdman KA, Burke LM. Position of the Academy of Nutrition and Dietetics, Dietitians of Canada, and the American College of Sports Medicine: Nutrition and Athletic Performance. J Acad Nutr Diet. 2016; 116(3):501-528. doi:10.1016/j.jand.2015.12.006.
8. Vitamin D and Muscle FunctionBeaudart C et al. The Effects of Vitamin D on Skeletal Muscle Strength, Mass, and Power: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. 2014; 99(11):4336-4345. doi:10.1210/jc.2014-1742.
9. Body-Composition Effects of Tirzepatide (SURMOUNT-1 Study)
Look M, Dunn JP, Kushner RF, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab. 2025; (ePub ahead of print). doi:10.1111/dom.16039.
10. Tirzepatide and Muscle Composition (MRI Analysis)
Tirzepatide and muscle composition changes in people with type 2 diabetes. Lancet Diabetes Endocrinol. 2025; (ePub ahead of print). doi:10.1016/S2213-8587(25)00027-0.
11. Semaglutide and Body Composition (12-Month Prospective Study)
van Baak MA, Brakema EA, Wijngaarden M van der, et al. Body composition and metabolic changes following 12 months of semaglutide 2.4 mg in adults with obesity: a prospective study. Diabetes Obesity and Metabolism. 2025; (ePub ahead of print).