Building Muscle While Losing Fat: TRT, GLP-1 Therapy, and Body Composition
One of the most frequent questions patients ask when considering GLP-1-based weight-loss treatment is whether losing a significant amount of weight also means losing muscle.
A 2026 study published in Obesity Pillars provides encouraging evidence that substantial fat loss can occur alongside improvements in estimated skeletal muscle mass and strength when medication is combined with appropriate support.
In “Increasing Skeletal Muscle Mass and Strength During Incretin-Based Weight Loss,” researchers followed 93 men with obesity and testosterone deficiency for up to 12 months. Participants received weekly tirzepatide and testosterone cypionate as part of a structured program that also emphasized resistance exercise, high-protein nutrition, and lifestyle coaching.
The findings provide an interesting look at what may be possible when medical weight loss focuses on body composition rather than scale weight alone.
Study Results at 12 Months
After 12 months, researchers reported:
Body weight decreased approximately 18% to 20%
Fat mass decreased approximately 38% to 40%
Estimated skeletal muscle mass increased approximately 4% to 12%
Grip strength increased approximately 18% to 21%
Total lean body mass decreased approximately 5% to 8%
The study also included men with type 2 diabetes and reported improvements in HbA1c among that subgroup. However, because Affinity Whole Health's medical weight-management programs are not designed to treat diabetes, the body-composition findings are more directly relevant to our clinical approach.
One of the most interesting aspects of the study is the distinction between lean body mass and estimated skeletal muscle mass.
Lean body mass includes skeletal muscle, organs, body water, connective tissue, and other non-fat tissues. As a result, a decrease in total lean mass does not necessarily mean an equivalent loss of functional skeletal muscle.
In this study, total lean body mass declined while estimated skeletal muscle mass and measured grip strength increased.
That distinction is important when evaluating the quality of weight loss.
An Important Limitation of the Study
The findings are encouraging, but they should not be interpreted as proof that TRT or any single component of the program was independently responsible for the improvements in estimated skeletal muscle mass and strength.
The study was a retrospective case series without a control group.
Participants received several interventions simultaneously:
Tirzepatide
Testosterone cypionate
Resistance-exercise guidance
High-protein nutrition
Lifestyle coaching
Because these interventions were used together, the study cannot determine how much of the observed improvement came from testosterone therapy, resistance training, nutrition, tirzepatide, or the combination of these factors.
The researchers also estimated skeletal muscle mass using bioelectrical impedance analysis rather than imaging techniques such as MRI or CT.
Larger prospective randomized studies are needed to determine the individual contribution of each intervention.
Why Body Composition Matters More Than the Scale
Losing weight can improve health, but the composition of that weight loss matters.
Ideally, a medical weight-management program should promote substantial fat loss while supporting skeletal muscle, strength, and physical function.
Muscle plays an important role in:
Strength and mobility
Physical function
Glucose metabolism
Metabolic health
Bone health
Exercise performance
Long-term weight management
This is why scale weight alone provides an incomplete picture of progress.
A patient can lose a significant amount of weight while also losing lean tissue. Conversely, someone may experience a slower change on the scale while achieving meaningful reductions in body fat and maintaining or improving muscle.
Tracking body composition helps distinguish between these outcomes.
Do GLP-1 Medications Cause Muscle Loss?
GLP-1-based medications can produce substantial reductions in body weight and fat mass. However, some of the weight lost during treatment can also come from lean body mass.
Clinical trials of incretin-based weight-loss medications have reported reductions in lean mass during treatment. The proportion varies considerably depending on the medication, patient population, amount of weight lost, nutrition, physical activity, and method used to measure body composition.
This does not mean that GLP-1 medications simply “cause muscle wasting.”
Lean body mass is not synonymous with skeletal muscle, and changes in hydration and other non-fat tissues can influence body-composition measurements.
The more useful clinical question is:
How can patients promote fat loss while supporting muscle mass, strength, and physical function during treatment?
Several factors may help.
The Role of GLP-1-Based Weight-Loss Therapy
Medications such as semaglutide and tirzepatide can produce significant reductions in appetite, calorie intake, body weight, and fat mass when prescribed to appropriate patients.
These effects can make them powerful tools for medical weight management.
But substantial weight loss creates an additional challenge: when calorie intake decreases significantly, the body may lose both fat and lean tissue.
Medication therefore should not be viewed as the only component of a body-composition strategy.
Adequate nutrition, resistance exercise, appropriate protein intake, and ongoing monitoring remain important throughout treatment.
Learn more about protein intake during GLP-1 weight loss.
The Role of Testosterone Replacement Therapy
Testosterone plays an important role in skeletal muscle physiology, strength, and body composition.
Men with clinically confirmed testosterone deficiency may experience symptoms and changes that include reduced energy, decreased libido, reduced muscle mass, changes in body composition, and impaired physical performance.
For men with clinically confirmed testosterone deficiency, appropriately prescribed testosterone replacement therapy may help support lean mass and strength.
TRT is not a muscle-preservation treatment that should automatically be added to GLP-1 therapy.
Whether testosterone replacement is appropriate depends on a patient's symptoms, laboratory results, medical history, risk factors, and evaluation by a qualified medical provider.
This distinction is particularly important because the men in the 2026 Obesity Pillars study had testosterone deficiency. The results should therefore not be generalized to men with normal testosterone levels.
Large randomized trials specifically evaluating TRT combined with GLP-1-based weight-loss therapy remain limited.
Read more about combining GLP-1 medications with testosterone therapy.
Resistance Training Is a Critical Part of the Equation
Resistance exercise provides a direct stimulus for the body to maintain and build skeletal muscle.
This becomes particularly important during significant weight loss.
A well-designed resistance-training program may include exercises targeting major muscle groups and progressive increases in resistance as strength improves.
The appropriate exercise program will vary according to age, physical condition, previous training experience, injuries, and other health considerations.
The goal is not necessarily bodybuilding.
It is to provide the muscles with a consistent reason to remain strong and functional while body weight decreases.
Protein Intake Matters During Weight Loss
Protein provides the amino acids necessary for maintaining and repairing skeletal muscle.
When appetite decreases significantly during GLP-1 treatment, patients may unintentionally reduce protein intake along with overall calories.
That makes dietary planning particularly important.
Protein requirements should be individualized based on factors such as body size, activity level, age, kidney function, overall health, and treatment goals.
Some weight-loss and resistance-training programs use protein targets around 1.6 g/kg per day, although this is not an appropriate universal target for every patient.
The emphasis should be on consuming enough high-quality protein to support individual nutritional needs while maintaining an appropriate overall calorie intake.
For a deeper discussion, read our guide to protein during GLP-1 weight loss.
Putting It Together: A Body-Composition Approach
For appropriate patients, high-quality weight loss may involve several complementary strategies:
GLP-1-based therapy when medically appropriate to support substantial and sustainable weight loss
TRT when clinically indicated for men with confirmed testosterone deficiency
Progressive resistance training to provide a stimulus for maintaining strength and skeletal muscle
Adequate protein and nutrition individualized to the patient's needs
Objective body-composition monitoring rather than relying exclusively on scale weight
Ongoing medical follow-up to evaluate response, side effects, laboratory results, and treatment goals
The 2026 Obesity Pillars study provides encouraging real-world evidence that substantial weight and fat loss can occur while estimated skeletal muscle mass and strength improve when these strategies are used together.
However, because the study did not include separate treatment groups, it cannot establish which individual component or combination of components produced those results.
Measuring Progress Beyond Body Weight
If preserving muscle is a priority, simply tracking pounds lost is not enough.
Body-composition analysis provides additional information about changes in estimated fat mass, lean mass, and skeletal muscle.
At Affinity Whole Health's in-person clinics, patients can receive free InBody body composition analysis as part of ongoing monitoring.
These measurements allow patients and providers to look beyond the number on the scale and evaluate whether changes are moving in the desired direction.
Body-composition measurements are still estimates and should be interpreted alongside other indicators, including strength, physical performance, laboratory results, symptoms, and overall health.
Clinical Perspective at Affinity Whole Health
At Affinity Whole Health, the goal of medical weight management is not simply to produce the lowest possible number on the scale.
For appropriate patients, we focus on preferential fat loss while supporting muscle, strength, physical function, and overall health.
GLP-1-based treatment may be incorporated into an individualized medical weight-management program when clinically appropriate.
For men who also have symptoms and laboratory findings consistent with testosterone deficiency, testosterone replacement therapy may be considered following appropriate medical evaluation.
We also emphasize resistance training, adequate protein intake, lifestyle habits, and body-composition monitoring throughout treatment.
This approach allows treatment to be adjusted based on more than scale weight alone.
Patients can also learn more about Affinity Whole Health's ongoing metabolic support.
The Bottom Line
Significant weight loss does not necessarily have to mean significant loss of functional muscle.
The 2026 Obesity Pillars study found that men with obesity and testosterone deficiency who participated in a structured program involving tirzepatide, testosterone cypionate, resistance exercise, high-protein nutrition, and lifestyle coaching experienced substantial reductions in body weight and fat mass while estimated skeletal muscle mass and grip strength increased.
Those results are encouraging, but they should be interpreted appropriately. The study was observational, lacked a control group, and cannot determine which component of the program was responsible for the observed changes.
The broader lesson is clear: body composition deserves attention during medical weight loss.
For appropriate patients, medication, resistance exercise, nutrition, hormonal evaluation, and objective monitoring can all play a role in pursuing weight loss that prioritizes fat reduction while supporting strength and muscle.
If you are considering GLP-1-based weight-loss therapy, already using one, or have concerns about testosterone levels and body composition, Affinity Whole Health can review your symptoms, laboratory results, medical history, and goals to determine an individualized approach.
Schedule your consultation today.
This content is for educational purposes only and does not constitute medical advice. Semaglutide, tirzepatide, and testosterone replacement therapy have specific indications, contraindications, risks, and monitoring requirements. Testosterone therapy should only be used when medically appropriate following evaluation by a qualified healthcare provider. Individual results vary.
Key Source
Mendias CL, Awan TM. Increasing Skeletal Muscle Mass and Strength During Incretin-Based Weight Loss. Obesity Pillars. 2026;19:100317.
https://www.sciencedirect.com/science/article/pii/S2667368126000732