GLP-1 Drugs Don't Fix Everything

[keangkong]

There have been a variety of scholarly articles extolling the virtues of GLP-1 drugs for treating a variety of ailments other than just diabetes and weight loss. Here is a rare negative article on GLP-1 drugs. It concludes that while people lose weight on GLP-1 drugs, their aerobic fitness appears not to improve.

Liu, et al. (2025). Incretin Receptor Agonism, Fat-free Mass, and Cardiorespiratory Fitness - A Narrative Review. J. Clin. Endocrinology & Metabolism 110(10), 2709-2717.

 

[nevets]

Skimmed the full paper and honestly not that surprised, they looked at dual GLP/GIP and triple GLP/GIP/glucagon and still showed lots of reductions in Fat Free Mass (FFM) loss. People who gain weight and get on these peptides can live their same sedentary lifestyle and it is not surprising that we see lots of lean body mass being lost if this lifestyle is maintained. Hopefully this motivates people to increase protein intake and start some resistance training. I attached a screenshot of the paper regarding some unknowns that they have acknowledged in the study.

 

[AndyPanda]

I think the solution to this is pretty simple. People need to lift weights. The problem is that these drugs work so well on sedentary people that they often don’t make lifestyle changes. If the only reason you had muscle mass was because you were carrying around extra weight, of course you are going to lose muscle as you lose weight. If you starve weight off, you will also gain it all back as soon as you start eating again. Probably even more. If exercise is part of your regimen, you will keep it off longer. Even body weight exercises like pushups and body squats are great for building and maintaining muscle.

 

[nevets]

Here’s a direct quote from the full paper regarding FFM.

“In the STEP trials evaluating semaglutide, FFM loss accounted for ∼40% of total weight loss (5, 42). Similarly, the SUSTAIN 8 trial revealed that, after 52 weeks of semaglutide treatment, total fat mass was reduced by 3.4 kg, while total lean mass decreased by 2.3 kg (44). In the SURMOUNT-1 trial, the dual GLP-1/ GIPRA tirzepatide reduced fat mass by 17 kg (33.9%) but also led to a 6-kg (10.9%) reduction in lean body mass(5, 45). Similarly, the GLP-1/GIP/glucagon receptor triagonist retatrutide demonstrated that approximately 33% of weightloss resulted from FFM reduction in phase II studies (5).”

 

[Nathanologist]

Here’s one showing that diet and exercise can help mitigate the glp-1 weight loss.

Resistance Training + Protein May Lower GLP-1 RA Muscle Loss

Supervised lifestyle intervention from a medical professional may help maximize fat loss and minimize muscle tissue loss in people taking the potent weight loss drugs.

www.medscape.com

Taking a GLP-1 agonist helps you lose weight, which is good for many health markers. But CRF isn’t just about being lighter. It’s about how well your heart, lungs, blood vessels, and muscles can perform.

To improve CRF (not just maintain it) you typically need an aerobic training stimulus (e.g., sustained moderate‐to‐high intensity cardio), plus muscle endurance/ strength work, and good nutrition (protein, micronutrients, recovery). Drug‐induced weight loss alone doesn’t provide that stimulus.

Body builders know this, many are using these drugs to enhance will power during cutting cycles. They stick to the muscle sparing workouts and diet while doing this. I bet you dollars to donuts if they were seeing a higher than normal % of lean mass loss from it they’d ditch the GLP-1 post haste.