Novo's Semaglutide May Preserve Lean Muscle Better Than Lilly's Tirzepatide
A new study found that tirzepatide removes 1.1% more lean body mass than semaglutide after three months, rising to 2% after a year. Both drugs cause some muscle loss, but the difference is clinically meaningful.
What This Means for You
A new study found that tirzepatide removes 1.1% more lean body mass than semaglutide after three months, rising to 2% after a year. Both drugs cause some muscle loss, but the difference is clinically meaningful.
A study comparing the effects of semaglutide (Wegovy, Ozempic) and tirzepatide (Zepbound, Mounjaro) on lean body mass has found that tirzepatide causes significantly greater muscle loss, according to Reuters.
After three months of treatment, patients on tirzepatide lost 1.1% more lean body mass than those on semaglutide. After 12 months, the gap widened to 2%. This is not an argument against tirzepatide — it still produces more total weight loss than semaglutide — but it does raise the question of what that weight loss consists of.
Muscle is metabolically active tissue. Losing it can lower your basal metabolic rate, making weight regain more likely if you stop the medication. The researchers recommended that patients on either drug incorporate resistance training and adequate protein intake to mitigate muscle loss.
Next-generation GLP-1s like Novo’s CagriSema (semaglutide + cagrilintide) are designed to produce weight loss while preserving more lean mass, which could be a key differentiator if early trial data holds up in larger studies.
Frequently Asked Questions
Should I switch from tirzepatide to semaglutide because of muscle loss?
Not necessarily. The total weight-loss advantage of tirzepatide remains significant — many patients see 5–10% more total body weight reduction than on semaglutide. The more important step is to add resistance training and ensure adequate protein intake while on any GLP-1.
How much muscle loss is normal on GLP-1s?
Studies suggest that 20–40% of total weight lost on GLP-1s can come from lean mass, not fat. This is higher than with diet and exercise alone. Resistance training two to three times per week and consuming 1.2–1.6 grams of protein per kilogram of body weight can help preserve muscle.
Will CagriSema really prevent muscle loss?
Early trial data on CagriSema suggests better muscle preservation than semaglutide alone, but the full Phase 3 data is not yet published. It is one of the most anticipated drugs in the pipeline, expected to be filed with the FDA in late 2026 or early 2027.
Source: Reuters
Frequently Asked Questions
Should I switch from tirzepatide to semaglutide because of muscle loss?
How much muscle loss is normal on GLP-1s?
Will CagriSema really prevent muscle loss?
Original source
Read the full article at Reuters