GLP-1 and Muscle Loss: How to Preserve Lean Mass During Weight Loss

March 16, 2026

This article is derived from the session “Preserving Muscle Mass During GLP-1 Therapy: Nutrition and Integrative Approaches” presented by Dr. Jaclyn Leong, Medical Director of the UCI Health Weight Management Program, at the ObesityHelp 2025 National Conference, where she discussed evidence-based nutrition, resistance training, and integrative strategies to support lean body mass during GLP-1 therapy.

GLP-1 medications like Ozempic, Wegovy, Mounjaro, Zepbound, and Saxenda are widely used for weight management. Along with their popularity has come concern about muscle loss on GLP-1 therapy.

At the 2025 ObesityHelp National Conference, Dr. Jaclyn Leong addressed the science behind GLP-1 muscle loss and shared practical strategies for protecting lean body mass.

She opened with an important clarification:

“Muscle loss is actually not unique. We actually see it with significant diets, we see it with bariatric surgery, and they’re actually pretty comparative.”

This context matters as muscle loss can occur with any significant weight reduction. The key question is how to minimize it.

What Does the Research Say About GLP-1 and Lean Body Mass?

Current evidence suggests that approximately 25 to 40 percent of weight loss on GLP-1 medications may come from lean body mass. However, this proportion is similar to what is seen after bariatric surgery or major caloric restriction.

She also noted that a significant portion of weight lost on GLP-1 medications may be regained within the first year if treatment is discontinued, highlighting the importance of sustainable muscle-preserving strategies.

Dr. Leong also highlighted an often overlooked benefit:

“GLP-1s can improve muscle quality by reducing fat infiltration to the muscle and enhancing insulin sensitivity.”

This means that even if some lean mass decreases, muscle quality may improve. She also reminded the audience that muscle is adaptable:

“The skeletal muscle is highly adaptive and it can modify all throughout life, so just because you lose it doesn’t mean you can’t regain it.”

This is reassuring for anyone concerned about long-term muscle health.

Why Muscle Protein Synthesis Matters

Muscle protein synthesis, or MPS, is the process of building new muscle proteins. Maintaining lean mass depends on the balance between muscle building and muscle breakdown.

A key regulator in this process is mTOR, often described as the molecular switch that turns on muscle building mode, especially after resistance training.

Leucine, an amino acid found in higher concentrations in animal protein, plays a critical role in stimulating mTOR and supporting muscle protein synthesis.

Understanding this biology helps explain why protein intake and resistance training are so important during GLP-1 weight loss.

How to Preserve Muscle While on GLP-1 Therapy

During her session, Dr. Leong shared clear, evidence-based strategies to protect lean body mass.

1. Eat Enough Protein

For individuals on GLP-1 medications, she recommends:

  • 1.6 to 2.2 grams of protein per kilogram of body weight per day
  • More than 2.2 grams per kilogram does not appear to provide additional muscle-building benefit.

Each meal should include:

  • At least 20 grams of protein
  • Up to 40 grams per meal
  • Older adults may benefit from closer to 40 grams

Protein should be evenly distributed throughout the day. Eating most of your protein in one meal is less effective than spreading it across multiple meals. Dr. Leong also recommends casein protein before sleep, such as yogurt or cottage cheese, to help reduce overnight muscle breakdown.

2. Follow a Traditional or Anti-Inflammatory Diet

Research shows that traditional dietary patterns and anti-inflammatory diets predict greater muscle mass and better muscle function over time.

These patterns emphasize:

  • Whole, unprocessed foods
  • Olive oil and omega-3 fats
  • Phytonutrient-rich vegetables and fruits
  • Reduced refined carbohydrates
  • Avoidance of processed meats and inflammatory oils

Returning to real, minimally processed foods supports both metabolic health and muscle preservation.

3. Prioritize Resistance Training

Aerobic exercise supports cardiovascular health and weight loss, but resistance training is the most effective tool for preserving muscle during GLP-1 therapy.

Key recommendations:

  • Perform 3 to 5 sets per exercise
  • Rest 3 to 5 minutes between sets
  • Train close to muscle fatigue, leaving one rep in reserve
  • Train each muscle group at least twice per week
  • Aim for 10 to 20 total sets per muscle group weekly

There is no magic number of repetitions. What matters most is training intensity and consistency. Dr. Leong also emphasized that recovery matters. Overtraining can impair muscle protein synthesis and limit progress, particularly in individuals under stress or with chronic health conditions.

The Bottom Line on GLP-1 and Muscle Loss

Preserving lean body mass during GLP-1 therapy is not about fear, it is about strategy. Muscle loss can happen with any significant weight reduction, but it is not inevitable or irreversible. With adequate protein intake, thoughtful meal distribution, resistance training, and attention to recovery, individuals can actively support muscle preservation while benefiting from GLP-1 treatment. As Dr. Leong emphasized, skeletal muscle remains adaptable throughout life. The focus should not be on avoiding weight loss, but on approaching it in a way that protects long-term strength, metabolic health, and overall well-being.

Frequently Asked Questions

Q1: Does everyone lose muscle on GLP-1 medications?

Some lean mass loss can occur, but it is proportional to weight loss and similar to other weight reduction methods. Resistance training and adequate protein reduce this risk significantly.

Q2: Can muscle be regained after GLP-1 weight loss?

Yes. Skeletal muscle is highly adaptive and can be rebuilt with consistent resistance training and sufficient protein intake.

Q3: Is resistance training more important than cardio for muscle preservation?

Yes. Aerobic exercise supports overall health, but resistance training is the primary driver of muscle maintenance and growth.

Dr. Jaclyn Leong is a triple-boarded physician in the disciplines of internal medicine, integrative medicine, and obesity medicine and currently serves as the Medical Director of the UCI Health Weight Management Program

Watch the full video of Dr. Jaclyn Leong's session below!

GLP-1 muscle loss

ABOUT THE AUTHOR

Dr. Jaclyn Leong is a triple-boarded physician in the disciplines of internal medicine, integrative medicine, and obesity medicine. She currently serves as the Medical Director of the UCI Health Weight Management Program, where she leads comprehensive, patient-centered care that supports sustainable health transformation.