Taking the question as asked, rather than the general version of it. 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.

labquiet_amy 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.

This matches mine closely enough to be worth saying so. 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.

Adding the clinical framing, because it changes how the question reads.

RunnerRach said:

...the muscle loss concern with lean mass...

This is a legitimate and well-studied concern. Let me put some numbers on it:

In STEP 1, approximately 39% of weight lost was lean mass. However, the Lundgren 2024 study showed that structured resistance training reduced this to ~25% lean mass loss.

Context matters: at BMI 35+, you're carrying excess lean mass to support the extra weight. Losing some lean mass is expected and not inherently harmful if you maintain adequate muscle function through exercise.

The solution isn't avoiding the medication — it's combining it with proper exercise and protein intake.