The Muscle Loss Problem with GLP-1 Medications (And What to Do About It)
You're losing weight on Ozempic, Wegovy, or Mounjaro. The scale is moving in the right direction. Your clothes fit better. Your health markers are improving.
But there's an aspect of GLP-1 weight loss that often goes unaddressed: a significant portion of that weight loss isn't fat. It's muscle.
When people lose weight rapidly—whether through GLP-1 medications, severe caloric restriction, or any other method—they typically experience some muscle loss alongside fat loss. This is normal physiology. But with GLP-1 medications specifically, recent research shows patterns that deserve attention.
What the Research Shows
A 2024 systematic review and meta-analysis published in Obesity examined body composition changes across multiple GLP-1 studies. The analysis found that participants lost an average of 2.6-3.6 kg of lean body mass (muscle, bone, organs) alongside their fat loss. While this might seem modest, it represents a significant proportion of total weight lost.
The STEP 8 trial, published in Cell Metabolism in 2025, provided even more detailed body composition data. Researchers found that participants who didn't engage in resistance training lost 39.4% of their total weight as lean mass—meaning nearly 4 out of every 10 kilograms lost wasn't fat.
This isn't unique to GLP-1 medications— rapid weight loss from any method typically results in 20-30% lean mass loss. But GLP-1 medications create particularly rapid weight loss, which can amplify this effect without proper intervention.
Why This Happens
GLP-1 medications work by mimicking a hormone that suppresses appetite and slows gastric emptying. You eat less—sometimes much less. This creates a caloric deficit that triggers weight loss, but your body doesn't distinguish between "good" weight loss (fat) and "problematic" weight loss (muscle).
When you're in a significant caloric deficit without adequate protein intake and resistance training stimulus, your body will break down muscle tissue for energy. It's not a medication side effect—it's a consequence of how our bodies respond to rapid weight loss.
The medication does its job (appetite suppression). But without additional strategies to preserve muscle, your body follows its default pattern: lose both fat and muscle during caloric restriction.
Why Muscle Loss Matters
Muscle mass isn't just about aesthetics or strength. Muscle is metabolically active tissue that:
Burns calories at rest - More muscle means higher metabolic rate
Regulates blood sugar - Muscle is your body's primary glucose disposal system
Protects bones - Muscle mass and bone density are closely linked
Maintains function - Muscle determines your ability to move, balance, and stay independent as you age
Predicts longevity - Research consistently shows muscle mass correlates with lifespan
A 2014 study in The American Journal of Clinical Nutrition followed over 3,600 older adults for nearly 6 years. Researchers found that higher muscle mass was associated with significantly lower all-cause mortality, even after adjusting for body weight and other health factors.
When you lose muscle during weight loss, you're undermining many of the health benefits you're trying to achieve.
What You Can Do About It
The good news: muscle loss during GLP-1 treatment isn't inevitable. Research shows clear strategies that work.
1. Prioritise Protein
A 2018 meta-analysis in British Journal of Sports Medicine examined protein requirements during resistance training and found that protein intake of 1.6-2.2g per kilogram of body weight optimized lean mass gains and preservation.
When your appetite is suppressed, protein needs to be non-negotiable. Every meal should be built around a protein source.
2. Resistance Training
The same 2024 meta-analysis in Obesity that documented lean mass loss also examined interventions. Studies that included resistance training showed significantly better preservation of lean mass compared to those without exercise.
In the STEP 8 trial, participants were randomized to different exercise interventions. Those who performed structured resistance training maintained substantially more muscle mass than those who didn't exercise, even when total weight loss was similar.
3. Adequate Caloric Intake
GLP-1 medications can suppress appetite so much that people eat far below what their body needs. While a caloric deficit is necessary for fat loss, research shows that excessively large deficits accelerate lean mass loss.
Establishing appropriate caloric targets—even while appetite is suppressed—helps maintain muscle while still losing fat.
4. Track Body Composition, Not Just Weight
The scale doesn't tell you what you're losing. DEXA scans, InBody measurements, or even simple progress photos and strength tracking give you better information.
If your weight is dropping but your strength is declining rapidly, that's worth investigating.
The Bottom Line
GLP-1 medications can be effective tools for weight loss. The research is clear on their efficacy for reducing body weight and improving metabolic markers.
But weight loss without muscle preservation isn't optimal. The goal isn't just to weigh less. It's to be stronger, healthier, and more functional at a lower body weight.
That requires intentional strategy around protein, resistance training, and body composition tracking.
If you're on GLP-1 medications (or considering them) and want to understand how to protect muscle mass during weight loss, I've created a free guide with five evidence-based strategies.
Weight loss is an investment in your health. Make sure you're getting the outcomes you want.
References:
Ida S, Kaneko R, Imataka K, Okubo K, Shirakura Y, Azuma K, Fujiwara R, Takahashi H, Murata K. Changes in Body Composition with GLP-1 Receptor Agonist Treatment: A Systematic Review and Meta-Analysis. Obes (Silver Spring). 2024 Jun;32(6):1054-1969. PMID: 38629387. https://pubmed.ncbi.nlm.nih.gov/38629387/
Lundgren JR, Janus C, Juhl Jensen SB, et al. Impact of semaglutide on body composition: The STEP 8 trial. Cell Metab. 2025. (Article in press) https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00331-6
Srikanthan P, Karlamangla AS. Muscle mass index as a predictor of longevity in older adults. Am J Clin Nutr. 2014;100(5):1214-1222. doi:10.3945/ajcn.114.089557
Morton RW, Murphy KT, McKellar SR, et al. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018;52(6):376-384. doi:10.1136/bjsports-2017-097608
Heymsfield SB, Wadden TA. Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med. 2017;376(3):254-266. doi:10.1056/NEJMra1514009
