GLP-1 and Hormone Therapy: A Dual Approach to Metabolic Health
For patients aiming to lose weight and improve metabolic health, compounded GLP-1 medications like semaglutide and tirzepatide are now widely recognized for their ability to suppress appetite and promote fat loss. However, an often overlooked but essential aspect of effective, sustainable weight management is the preservation of lean muscle mass, which requires healthy hormone levels.
At Affinity Whole Health, we’ve seen significant success combining these two therapies. When used together, GLP-1s and hormone therapy (often referred to as HRT or TRT) can create a balanced and powerful strategy for fat loss, muscle retention, and long-term wellness.
Dr. Koehler, MD explains the science (60 seconds)
How GLP-1 Medications Work
GLP-1 receptor agonists such as compounded semaglutide and compounded tirzepatide help regulate appetite by slowing gastric emptying and reducing cravings. This allows patients to:
Feel full longer
Cut caloric intake without hunger pains or food noise
Make healthier food choices
Reduce binge and impulse eating
While many patients experience significant weight loss with GLP-1s, weight loss is not always synonymous with fat loss. Without the right support, including proper diet, strength training, and hormone balance, individuals can lose lean muscle mass alongside fat.
Why Losing Muscle Is a Bad Thing
When patients lose weight too quickly or without proper support, a significant portion of that loss can come from muscle mass rather than fat. This is problematic for several reasons:
Slower Metabolism: Muscle tissue is metabolically active, meaning it burns calories even at rest. Losing muscle lowers your basal metabolic rate, making it harder to keep weight off long-term.
Higher Risk of Regain: With fewer calories burned daily, the body becomes more prone to regaining fat once normal eating patterns resume.
Weaker Strength & Performance: Muscle loss leads to decreased strength, endurance, and exercise capacity, limiting your ability to stay active and fit.
Bone & Joint Health: Lean muscle supports bones and joints. Without it, patients face increased risk of osteoporosis, joint pain, and injury.
Metabolic & Hormonal Impact: Reduced muscle mass is linked to insulin resistance, type 2 diabetes, and cardiovascular issues—making muscle preservation critical for overall metabolic health.
Simply put, losing muscle undermines both short-term results and long-term health. That’s why pairing GLP-1 medications with hormone therapy, strength training, and proper nutrition is essential for true body recomposition—not just weight loss.
What We Monitor and Measure
At Affinity Whole Health, we do more than track weight on the scale. We offer advanced InBody scans that give a full picture of:
Body fat percentage
Skeletal muscle mass
Basal metabolic rate (BMR) or how many calories your body needs in order to function
Visceral fat levels
This approach helps ensure that weight loss is truly beneficial—reflecting fat loss rather than a reduction in healthy, metabolically active tissue. In fact, many men and women on hormone therapy see their body fat drop while their skeletal muscle increases—even if the scale doesn’t move dramatically; combining hormone therapy and GLP-1s can accomplish both.
The Role of Testosterone in Weight Loss
Testosterone is essential for muscle protein synthesis, which means it is directly responsible for building and maintaining muscle tissue. For patients using GLP-1s, caloric restriction can lead to undesirable losses in both muscle and bone mass.
When testosterone is optimized, it helps the body:
Preserve and build lean muscle mass
Improve metabolism and resting calorie burn
Maintain bone density
Enhance exercise performance and recovery
This makes it a valuable counterbalance to GLP-1’s calorie-reducing effects.
Why the Combination Works
The synergy of GLP-1 medications and hormone therapy (for those with hormone deficiency or hormone imbalances) creates an ideal environment for safe, sustainable body recomposition. GLP-1s help patients reduce body fat by lowering calorie intake, while hormone therapy ensures that muscle and strength are preserved throughout the process. Learn more about the effects of testosterone treatment on body fat here.
Recent findings underscore the potential of hormone therapies to amplify the metabolic benefits of GLP-1s. For example, in a study highlighted by Medscape involving menopausal women on tirzepatide, those who were also taking hormone therapy lost significantly more weight than those who weren’t—suggesting that sex hormone optimization may be a powerful enhancer of GLP-1’s efficacy. While this study focused on women and estrogen, the broader principle applies: correcting underlying hormonal imbalances can significantly boost the impact of GLP-1 therapy.
This is especially important because muscle mass is one of the most important predictors of long-term metabolic health. More muscle not only means a higher basal metabolic rate but also reduces risk for insulin resistance, type 2 diabetes, and cardiovascular disease.
Coaching for Long-Term Success
We coach our patients to aim for gradual, sustainable weight loss. Faster weight loss may cause muscle breakdown or other unwanted side effects.
We also recommend a practical, flexible approach to nutrition and lifestyle:
Prioritize high-protein intake at every meal or snack
Stay well hydrated (especially since GLP-1s can reduce fluid intake and alcohol desire)
Include fiber to support digestion
Avoid aggressive calorie counting—focus on quality choices
Prioritize both strength training and cardiovascular exercise
These simple guidelines help support a healthier body composition while improving patient adherence and satisfaction.
Individualized Dosing Is Key
Every patient is different, which is why we avoid a one-size-fits-all approach. “There is no ‘goal dose’ for GLP-1s. The right dose is the lowest effective dose that gives appetite suppression without causing side effects,” said Dr. Michael Koehler. Some patients may require lower or higher doses depending on GLP-1 sensitivity.
Hormone therapy is also individualized. While some feel best with higher free testosterone levels, others thrive in the mid-range. That’s why we combine lab testing with symptom tracking to make sure each patient is on the right protocol for their body and goals.
The Bottom Line
GLP-1 medications are highly effective for fat loss, but they can lead to muscle loss without the right strategy in place. Hormone therapy helps preserve lean mass, optimize metabolism, and support overall wellness during weight loss. When combined, these therapies provide a scientifically grounded, patient-centered approach to metabolic health transformation.
At Affinity Whole Health, we believe in more than weight loss—we focus on helping patients build strength, energy, and long-term health from the inside out.