Glucagon-like peptide-1 (GLP-1) receptor agonists have been making headlines for their dual role in managing type 2 diabetes and facilitating weight loss. As their use becomes increasingly widespread thanks to high-profile drugs like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), questions about their long-term safety, efficacy and impact on body composition remain at the forefront. A new study from researchers at the University of Hong Kong, published in Diabetes, Obesity and Metabolism, brings much-needed clarity to one of the most oft-cited concerns: Do GLP-1 receptor agonists cause muscle loss along with fat loss?

The short answer, according to this genetic analysis of more than 800,000 individuals, is yes—but significantly less than fat loss. The researchers confirmed that while both lean and fat mass are reduced during treatment, the reduction in fat mass is more substantial, resulting in an overall favorable change in body composition.

Let’s break down the findings, provide context from previous research, and examine how, as a health and exercise professional, you can use this information to better support your clients.

Understanding GLP-1 Receptor Agonists

GLP-1 receptor agonists mimic the effects of the natural GLP-1 hormone, which stimulates insulin secretion, suppresses glucagon, delays gastric emptying and promotes satiety. These mechanisms collectively improve blood glucose control and encourage weight loss by reducing appetite and calorie intake.

Initially developed for managing type 2 diabetes, GLP-1 drugs have rapidly gained popularity as weight-loss interventions due to their remarkable effects on body mass index (BMI). This shift in use was largely propelled by findings from pivotal clinical trials like STEP (Semaglutide Treatment Effect in People with Obesity) and SURMOUNT (the brand name of Eli Lilly’s clinical trial program). The STEP trials evaluated semaglutide and showed average weight reductions of around 15% over 68 weeks, while SURMOUNT trials—focusing on tirzepatide, a dual GIP/GLP-1 receptor agonist—demonstrated even greater reductions, with participants losing up to 21% of their body weight over 72 weeks (Note: GIP = Glucose-dependent insulinotropic polypeptide). These results far exceed what is typically achieved through lifestyle modification alone, where sustained weight loss often falls in the 5 to 10% range even with intensive intervention. In fact, the outcomes from SURMOUNT approach the levels of weight reduction historically only seen with bariatric surgery.

While these studies show the efficacy of these drugs, it’s still not clear whether the weight lost through GLP-1 drugs consists of fat, muscle or both. Loss of lean body mass, especially muscle, can contribute to frailty, sarcopenia and metabolic decline, all of which are particularly troubling in aging populations or individuals with low baseline muscle mass.

The Genetic Approach: A Novel Insight

The researchers at the University of Hong Kong used a method called Mendelian randomization, which analyzes naturally occurring genetic differences to mimic the effects of a drug—in this case, GLP-1 receptor agonists. They applied this approach to genetic data from more than 800,000 people of European ancestry to better understand how these medications influence body composition over time. They identified a specific genetic variant, rs877446, that mimics the effects of GLP-1 receptor agonists by being associated with lower BMI.

By analyzing how this variant influenced different body-composition measures, the researchers could simulate the long-term effects of GLP-1 drug use without relying solely on short-duration clinical trials. The measures included:

• Appendicular and trunk fat-free mass (proxy for lean muscle)
• Whole-body and trunk fat mass
• Body-fat percentage
• Waist-to-hip ratio

Key Findings

The researchers found that for every 1-unit reduction in BMI linked to GLP-1 mimicry:

• Fat mass decreased by ~7.9 kg
• Lean mass (muscle) decreased by ~6.4 kg
• Body-fat percentage dropped by ~4.5%

In other words, fat loss exceeded muscle loss in both absolute and relative terms, which supports the use of GLP-1 drugs as a viable treatment for obesity.

The team acknowledged that muscle mass loss is not negligible, but the preservation of a greater proportion of lean mass relative to fat is promising. According to Dr. Dipender Gill, a coauthor of the study from Imperial College London, this genetic methodology offers a “timely and cost-efficient” way to predict drug effects and guide future clinical trials.

Context From Previous Research

These findings align with earlier clinical studies, although they had more limited follow-up durations. For example:

• The STEP 1 trial, published in The New England Journal of Medicine in 2021, found that semaglutide led to significant weight loss and improvements in metabolic markers, with secondary data suggesting modest reductions in lean mass.
• A 2022 meta-analysis published in Obesity Reviews found that participants taking GLP-1 receptor agonists typically experienced 25 to 40% of their weight loss from lean mass—within an expected and manageable range when considering dietary interventions or bariatric surgery.

What sets this latest study apart is its robust use of large-scale genetic data to assess long-term, population-wide impacts, rather than relying solely on short-term clinical follow-up.

How to Apply the Findings as a Health and Exercise Professional

As a health and exercise professional, these findings present you with both opportunities and challenges. As more clients consider or begin using GLP-1 medications, it becomes essential to adapt strategies and expectations accordingly.

1. Combatting Muscle Loss Through Resistance Training

Even though GLP-1 drugs favor fat loss, the concurrent reduction in muscle mass cannot be ignored. Health professionals should prioritize resistance training and progressive overload in clients on these medications. Exercise programming should emphasize:

• Multijoint movements (e.g., squats, deadlifts, presses)
• Regular strength assessments and progress tracking
• Adequate rest and recovery to prevent overtraining in deconditioned clients

GLP-1 users may also experience reduced energy intake, so recovery nutrition and protein timing become more crucial.

2. Nutritional Counseling and Protein Intake

While outside the strict scope of practice for most health and exercise professionals, you can collaborate with registered dietitian nutritionists to ensure that your clients maintain adequate protein intake—generally 1.2 to 2.0 grams per kilogram of body weight, depending on training status and goals.

Encourage your clients to track protein intake and consider meal frequency and timing to maximize muscle protein synthesis, particularly in older adults or those undergoing significant weight loss.

3. Managing Expectations and Long-term Planning

As highlighted in other ACE resources, clients often have unrealistic expectations about weight loss solving deeper psychological or lifestyle issues. This is particularly relevant for GLP-1 users, whose weight loss may be rapid and dramatic.

As a health and exercise professional, you can support your clients by:

• Regularly revisiting their goals and expectations
• Encouraging journaling and reflection exercises
• Celebrating non-scale victories like increased energy, stamina or strength

GLP-1s should be viewed as one tool in a larger health strategy—not a cure-all.

4. Understanding the Broader Impacts

Finally, health coaches and exercise professionals should be aware of the psychological and societal dynamics at play. Clients who lose weight on GLP-1s may experience changes in how others treat them or how they see themselves, sometimes leading to unexpected emotional responses.

Be ready to offer empathy, active listening, and referrals to mental health professionals if deeper issues arise.

Final Thoughts

This new study strengthens our understanding of GLP-1 receptor agonists as effective tools for weight management that primarily reduce fat rather than muscle mass. This is an important reassurance for clients and professionals alike, especially those concerned with preserving muscle for performance, function or metabolic health.

For health and exercise professionals, the take-home message is clear: These drugs can offer a supportive foundation for behavior change, but your role in helping clients build strength, maintain muscle, and to develop healthy habits remains indispensable. In fact, the combination of pharmacological and lifestyle interventions may represent the most powerful path forward in the fight against obesity and its related chronic conditions.

As GLP-1 therapies continue to evolve, your guidance, education and programming will be key in helping clients translate short-term changes into long-term health.

Expand Your Knowledge

A Guide for Supporting Clients on Anti-obesity Medications

Gain essential knowledge and skills to effectively support clients taking anti-obesity medications (AOMs) and navigate the evolving health and fitness landscape. This interactive course combines engaging video content and practical learning activities to equip health and fitness professionals with a comprehensive understanding of anti-obesity medications (AOMs) and their significant implications for clients, fitness professionals and the broader health and fitness industry. You’ll explore the physiological effects of AOMs, common challenges faced by clients using these medications and the best practices for creating programs for clients taking AOMs to improve adherence and achieve optimal outcomes. Also addressed are the biases and misconceptions that may exist within the fitness industry regarding AOMs. By adopting a client-centered approach and utilizing accurate, evidence-based information, professionals can confidently support their clients in achieving their health goals. 

 

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