Do weight-loss shots like Wegovy make you lose muscle too?

Short answer

Yes. But the share of lost weight that came from lean mass (25-35%) was no different from dieting, and it dropped to 17.5% when strength training was added to the diet.

Do weight-loss shots like Wegovy make you lose muscle too?
'Shot → less fat → much less muscle' — does this formula hold?
Many say that losing weight with shots like Wegovy (semaglutide) or Mounjaro (tirzepatide) melts your muscle. We checked how much muscle goes, and whether more goes than when you diet.
Lean mass did go down
With semaglutide, 5.44 kg more than with a placebo
An analysis that pooled 821 people on these shots found lean mass (muscle and everything except fat) fell 1.74 kg more on average than in the placebo groups. For semaglutide alone it was 5.44 kg. Muscle does come off along with fat.
But its share of the body went up
Because far more fat came off
In the same analysis, the share of body weight made up of lean mass rose 1.81 percentage points more than with a placebo. Far more fat than muscle was lost. In terms of body makeup, people ended up with a higher muscle share after the shots.
How does it compare with dieting?
The muscle share of lost weight was no different
An analysis that pooled 20 trials and 15,782 people found lean mass made up 35.2% of the weight lost on semaglutide and 25.4% on tirzepatide. Taken together, the shots were no different from diet and lifestyle groups (26.2%).
What about the muscle that was left?
Fat inside the muscle actually went down
In an MRI study of 246 people over 52 weeks, thigh muscle on tirzepatide shrank by 0.64 L, no different from what is expected for the same weight loss. Fat inside the muscle fell more than expected. In a study of 55 people over 72 weeks, 30-second sit-to-stands went from 13 to 15.
Strength training made the difference
Adding it cut the muscle share to 17.5%
In the same 15,782-person analysis, groups that added strength training to their diet had the lowest lean mass share of lost weight, at 17.5%. When 195 people combined the shot with exercise for 1 year, body fat percentage fell 3.9 points, about 2 times the shot-only group (1.9 points).
Bottom line: muscle goes, but it's not the shot's fault
It goes in the usual share for the weight lost
Weight loss on these shots lowers lean mass too, but its share of the lost weight (25-35%) was no different from dieting. Strength training shrank that share. People who also exercised weighed 5.1 kg less than the shot-only group even 1 year after stopping.