This one has a reasonably settled answer, so here it is. The intervention that works is boring and well evidenced: resistance training two to three times a week at a genuine effort, protein at 1.4 to 2.0 g/kg of reference body weight, and not making the deficit larger than the training can support. Cardio does not protect lean mass and in a deep deficit competes with recovery.

Dr.LipidDallas said:

The intervention that works is boring and well evidenced: resistance training two to three times a week at a genuine effort, protein at 1.4 to 2.0…

Agreed on the ranges, with the condition that a single DEXA is not a measurement, it is one draw from a distribution. Hydration status moves the lean compartment by a kilogram or more between scans, so any comparison of scans done at different times of day or different hydration states is noise.

RunnerRach said:

I lifted three times a week throughout and still lost lean mass.

Can confirm the pattern RunnerRach describes. The honest range is roughly 20 to 40% of total loss as lean mass without deliberate resistance training, and roughly 10 to 20% with it plus adequate protein. Both numbers need a caveat that matters: "lean mass" on a DEXA is not muscle. It includes water, glycogen and the lean fraction of organs, and glycogen alone carries about three grams of water per gram. A large early lean drop is mostly the glycogen and water going, which is why the first scan flatters and the second is the honest one.

If somebody has the primary source to hand I would rather cite it than paraphrase it.

Clinical perspective, offered as context rather than as advice.

My endo's protocol for lean mass plateau: if weight loss stalls for 6+ weeks at current dose, we go through this checklist before titrating up:

1. Food diary review — is intake creeping up?
2. Protein check — minimum 100g/day
3. Activity audit — steps + resistance training
4. Sleep quality — poor sleep kills GLP-1 efficacy
5. Stress/cortisol management

Only after addressing all of these do we increase the dose. Often fixing one lifestyle factor restarts progress without needing more medication.