Consider a patient lost 17 kg on semaglutide. While this represents treatment success, the question is what the relative contribution of fat loss and muscle loss was. In the STEP 1 trial, nearly 7 kg of the weight lost was lean tissue, not fat. Experts estimate that people in the semaglutide and tirzepatide trials lost at least a tenth of their muscle mass during the 68 to 72 weeks therapy, which is equivalent to 20 years of age-related muscle loss. [1]
This is not alarming, losing some muscle is normal whenever someone loses a lot of weight. A 2025 review found that the share of muscle lost on GLP-1 medicines closely resembles that observed with diet-induced weight loss. [2] The catch is that most trials lacked assessment of muscle strength or walking speed, so we do not yet know if it causes clinically meaningful impairments. [2]
Some people have less room for error: older adults, people who have had diabetes for many years or who have kidney disease, and anyone losing weight fast while eating little protein. [2] It also matters if the GLP-1 therapy is stopped, because the weight regained tends to be mostly fat, not muscle. [1]
Start with protein
These medicines work by suppressing appetite. It means reduced food intake, together with protein insufficiency. Four US obesity and nutrition societies recommend 1.2–1.6 g of protein per kilogram of body weight each day while someone is losing weight, using an adjusted weight for people with obesity. [3] Yet in a survey of people on GLP-1 therapy, fewer than half managed even the low end of that range. [4]
Timing helps too. Muscle uses protein best in steady doses of about 20–25 g at a time, so it makes sense to spread protein across meals rather than saving most of it for dinner. [2] When appetite is small, eating the protein on the plate first means it does not get left behind. [3] If food alone is not enough, nutrition drinks can help fill the gap without undoing the weight loss. [1] Supplements such as leucine, HMB, creatine and omega-3 have some evidence behind them, but none has been tested in people taking these medicines. [2]
The scale can’t tell you whether you’ve lost fat or muscle.
Give muscle a reason to stay
Protein gives the body the raw material for muscle. Strength training tells the body it still needs that muscle. Extra protein on its own probably will not be enough, [3] but strength training has been shown again and again to protect muscle while people cut calories. [1] Strength exercises at least three times a week, plus 150 minutes of moderate activity such as brisk walking is recommended. [3]
The benefits go beyond muscle. In a Danish study, people who took liraglutide and exercised kept their bone density, while those who took the medicine alone lost some bone at the hip and spine. [5]
Check, don’t guess
A body-composition scan (DXA, or a bioimpedance scale if DXA is not available) at the start, repeated as the weight comes off, can show early on if too much muscle is lost. [2,3] Simple checks such as grip strength, standing up from a chair or walking speed add useful information, and a reduction in muscle strength can show up before it appears on a scan. [1–3]
What’s next
New medicines that block the signals holding back muscle growth (activin and myostatin) are being tested alongside GLP-1 drugs. In early results from one trial, adding a drug called trevogrumab to semaglutide cut lean-mass loss roughly in half, from 6.5% to 3.3%. [2] But none of these are ready for routine use, and we do not yet know whether more muscle on a scan means people actually feel stronger or move better. [2]
For now, the best way to preserve muscle mass is simple: see a dietitian, set a protein goal, start strength training at therapy initiation, and check muscle as well as weight. Losing weight is the headline. Keeping muscle, which helps the body burn energy and makes the new weight easier to hold, is what makes it last. [1,3]