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Emerging Data About Combining GLP-1 Agonists with Myostatin Inhibitors
Benefits and Risks
Type-IIxJul 31, 2025
Author
Cormac J. Mannion (Type-IIx)Date
July 31, 2025
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Introduction
GLP-1 agonists work. That's not debatable. Semaglutide (GLP-1) and tirzepatide – the incretin peptides – drop bodyweight fast, and the data supports their effectiveness for weight management. But here's the caveat: without lifting weights (resistance training), without adequate protein intake, or otherwise without some other intervention – which we'll discuss now – about 35% of that weight loss comes from lean muscle tissue, not fat. [1].This is a problem! Despite evidence that semaglutide enhances insulin sensitivity to spare protein losses, the extreme caloric restriction that typifies severe energy restriction, such as when your appetite becomes so blunted by semaglutide that you're practically starving without noticing – or more importantly for an enhanced bodybuilder – without eating sufficient protein (and carbohydrate!) or training progressively and intensely (that only adequate carbohydrate makes possible), what inevitably happens is muscle loss. [2]. [3].
Despite the seemingly inapposite patient population for incretin peptides… the obese, the diabetic… who, quite unlike bodybuilders, are characterized by physical inactivity, to put it bluntly – there is evidence that even minor interventions like:
- encouraging them to walk or get an hours' exercise a couple days per week, and
- making sure they eat enough, maintaining scale weight reductions of no more than 1 lb weekly
Figure 1 – Virtually no muscle loss with simple encouragement to exercise and only lose 1 lb weekly ("lifestyle intervention")… and yes, that is good ol' insulin building muscle (green arrow). [4].
Now think – if a couple thousand steps a week, maybe some light calisthenics, the occasional pink dumbbell being lifted – and remembering to eat lunch – can make such a difference, you can safely bet the farm that a serious bodybuilder can stave off these muscle losses when he's doing everything he needs to!
So we simply cannot be complacent.
These drugs, left unchecked, can and will hinder your efforts at improving your physique. The COURAGE trial data makes this crystal clear – patients on semaglutide alone (inactive and starving) lost 7.9 pounds of lean mass out of 23 total pounds lost. [1-1].
Myostatin inhibitors offer yet another solution – indeed, an opportunity. These compounds block the body's natural brake on muscle growth, and when you combine them with GLP-1 agonists, something interesting happens: The muscle-wasting effect of severe caloric restriction arising out of the GLP-1 effects is not only neutralized in sedentary patients… but real recomp occurs – the holy grail of increased muscle mass and decreased fat mass, simultaneously. [5].
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