Weight Loss with GLP-1 Drugs Does Not Cause Excessive Loss of Muscle Mass or Muscle Function

RetCurious

RetCurious

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Summary

Because glucagon-like peptide-1 (GLP-1) medicines produce such a large drop in body weight, there is concern that lean body mass (LBM) and skeletal muscle might be lost. This work presents four pre-clinical studies plus a proof-of-concept clinical trial that speak to that question. In obese mice, we report, GLP-1 medicines mainly lower body fat, with a small yet significant reduction in LBM. Of the lean tissues, the decline in liver mass is greater than the change in muscle mass. Although absolute muscle mass and strength go down, relative muscle mass and strength go up, which yields better running performance. Notably, GLP-1 medicines affect the muscle proteome differently than calorie restriction does, even though atrophy during immobilization is comparable. In patients with obesity, GLP-1 medicines improve body composition without harming strength. Taken together, in middle-aged mice and men, GLP-1 medicines produce a slight drop in absolute muscle values while having a positive effect on body composition and mobility.


https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00082-0#
 
Excellent news! For decades I have done strength training, and the drop in LBM I see is no more than what calorie restriction alone would cause. On the whole, it is very slight. My strength has gone down, yes, but the muscle itself remains.
 
While using reta, my muscle growth has honestly been greater than what I saw throughout the whole prior year. Whether that comes from improved body recomp on reta, or from the fact that I spent that year on keto and am now taking in more carbs and protein, I can't say. What I can say is that I don't appear to be losing muscle at all, and the only training I've done during this entire period has been light weight work.
 
RetCurious said:

Now I'm wondering whether the whole "more protein" recommendation is still sound...
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In what way?

I underwent two DEXA scans, on 1/30 and 3/25. The results showed an 18.7lb reduction, of which .5lb was lean mass. That falls within the scan's margin of error—for instance, the same scans reported a 100g drop in bone mineral content and a 155g gain in visceral fat that covered 17% more area... both of which are highly improbable.
 
woundcarping said:

RetCurious said:

Now I'm wondering whether the whole "more protein" recommendation is still sound...
Click to expand...
In what way?

I underwent two DEXA scans, on 1/30 and 3/25. The results showed an 18.7lb reduction, of which .5lb was lean mass. That falls within the scan's margin of error—for instance, the same scans reported a 100g drop in bone mineral content and a 155g gain in visceral fat that covered 17% more area... both of which are highly improbable.
Click to expand...
Isn't the whole point of pushing more protein that we're trying to stop muscle mass from being lost?

So if losing muscle mass matters less, does that also mean getting more protein matters less?

I'll admit it: hitting my "recommended protein intake" is still a battle for me. 😆

Protein in my meals is something I enjoy, but I'd rather keep my meals balanced with fruits and vegetables.

While on reta, I notice I lean even more toward fruits and veggies.
 
RetCurious said:


The focus on higher protein intake revolves around preventing loss of muscle mass, no?

If muscle mass loss is less of a concern does it follow that higher protein intake is less of a concern?

Yes, I'm still struggling to get my "recommended protein intake". 😆

I like protein in my meals but I prefer balancing meals out with fruits and vegetables.

On reta I find I'm even more inclined toward fruits and veggies.

Click to expand...
Click to expand...

A lot of folks repeat a daily protein number—1g per pound of body weight—because they heard it somewhere, not because they looked into it. The reference point varies: some use the weight you are now, others use the weight you want to be.

If I used my current weight at 1g/lb, that would mean 240g of protein every single day. To get there I would need 2.3lb of ribeye or 12 cans of tuna at 5oz each, daily. My muscles simply cannot make use of 240g of protein per day.

My lean mass is 153lb. Working from that, my floor is 130g/day and my ceiling is about 220g/day. I aim for 150+g/day. Going above the ceiling doesn't bother me—it's effectively wasted and not worth the effort. I try not to dip below my floor on a regular basis, though it does happen.



When it comes to catabolic protection, here's what I do:

Reta instead of Tirz for the theoretical lean mass preservation

TRT—clinically hypogonadal, began TRT roughly 5 weeks into my cut.

beta‑hydroxy beta‑methylbutyrate (HMB-FA)—3g/daily

Resistance training—inconsistent, mostly skipped for the last month, need to return to the gym on a regular schedule.

D3k2-7—supplement, bloodwork showed low levels, can influence training performance

With that overall approach, per DEXA scans, between 1/30 and 3/25 I dropped 18.7lb, and just .5lb of that came from lean mass.

I'll introduce creatine in the coming weeks, once my water shift settles after adjusting my test dose according to labs. My next DEXA is planned for late next month.
 
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