Interesting article about the risks of using semaglutide for weight loss in healthy people.
from the information we can scrape together based on sub-cohort data, these “miracle drugs” start to look a bit less miraculous. In 2021’s STEP 1 trial – the first and only trial demonstrating the efficacy of semaglutide as a treatment for adult obesity – a subset of 140 patients underwent DEXA scans for body composition analysis. Among these patients, lean mass accounted for approximately 39% of total weight loss – substantially higher than ideal. In a substudy of 178 patients from the SUSTAIN 8 trial on semaglutide as a diabetes treatment, the average proportion of lean mass loss was nearly identical at 40%, despite lower doses and less total weight loss than in the STEP 1 trial.
While those with obesity stand to reap considerable health benefits from fat loss, the potential benefits of fat loss among healthy-weight individuals are minimal and are unlikely to offset the sizable health risks associated with reduced lean mass. Further, because the only large-scale trials of GLP-1 agonists have been conducted in obese or overweight study populations, we don’t yet know if these drugs affect body composition in normal-weight individuals in an equivalent manner.
Has anyone using those compounds noticed any muscle loss?
Basically, when we take these drugs we become less hungry, we don’t do resistance training and/or eat enough protein, so the lean mass loss is higher. From Peter’s article:
Increasing weight-bearing exercise and strength training can help to counteract losses in muscle and bone mass while taking these drugs, and patients should be careful that they’re consuming sufficient protein in spite of the overall reductions in appetite and calorie intake.
But significant loss of lean mass is going to happen with all weight loss programs that involve successful caloric restriction unless resistance training and adequate protein intake are maintained. It’s not unique to this new class of drugs. It’s a warning all people should get before being put on weight loss meds, weight loss surgery or any kind of calorie restricted diet IMO.
I guess we’ll see if there’s some other physiological mechanism that specifically causes lean mass loss with these drugs, but my understanding was that the final weight loss mechanism is simply decreased appetite and hence decreased caloric intake. As Attia mentioned, there’s a paucity of data so far.