Does Ozempic (Semaglutide) Cause Muscle Wasting?
Yes, semaglutide (Ozempic) can cause muscle wasting, particularly in older adults and those at risk for sarcopenia, as demonstrated by recent clinical evidence. 1
Evidence for Muscle Loss with Semaglutide
Clinical Studies
A 24-month retrospective cohort study found that semaglutide treatment significantly reduced muscle mass in older adults with type 2 diabetes compared to controls 1
Key findings from this study included:
- Decreased appendicular skeletal muscle mass index (ASMI)
- Reduced grip strength (particularly in women)
- Decreased gait speed in both genders
- Higher semaglutide doses were associated with greater muscle loss 1
Another study (SLIM LIVER) showed that people with HIV receiving semaglutide experienced a 9.3% decrease in psoas muscle volume over 24 weeks 2
Mechanism of Action
The International Antiviral Society-USA panel notes that "loss of muscle mass, a particular concern in older people at risk for sarcopenia, may occur with glucagon-like peptide-1 receptor agonist therapy" 3
Contradictory Evidence
Not all studies show muscle loss with semaglutide:
A study of Japanese patients with type 2 diabetes found that 24-week treatment with oral semaglutide reduced body fat without significantly changing whole-body lean mass or appendicular skeletal muscle index 4
Animal studies suggest that GLP-1 receptor agonists like liraglutide and semaglutide may actually protect against obesity-induced muscle atrophy via the SIRT1 pathway 5
Risk Factors for Muscle Loss
Patients at highest risk for semaglutide-induced muscle wasting include:
- Older adults (particularly those over 65)
- Those with pre-existing sarcopenia
- Patients receiving higher doses of semaglutide
- Individuals with low baseline muscle mass and function 1
Clinical Implications
Monitoring Recommendations
For patients on semaglutide therapy:
- Assess baseline muscle mass and function before initiating treatment
- Monitor for signs of muscle loss during treatment, particularly in high-risk patients
- Consider periodic assessment of grip strength and gait speed
- Be vigilant for functional decline that may indicate sarcopenia
Mitigation Strategies
- Consider nutritional supplementation with adequate protein intake
- Implement resistance training programs to preserve muscle mass
- For high-risk patients, consider lower doses of semaglutide when possible
- Balance the benefits of weight loss against the risks of muscle loss
Weight Loss Composition
The American Gastroenterological Association (AGA) clinical practice guideline notes that semaglutide 2.4 mg produces significant weight loss, with 64.9% of patients achieving ≥10% total body weight loss 3. However, this guideline does not specifically address the composition of this weight loss (fat vs. muscle).
Conclusion
While semaglutide is highly effective for weight management and cardiovascular risk reduction, clinicians should be aware of its potential to cause muscle wasting, particularly in vulnerable populations. The benefit-risk assessment should consider the patient's age, baseline muscle status, and overall health goals.