Myostatin, Activin A and Activin B are related proteins produced throughout the body, that together act as a biological brake on muscle growth. Evolutionarily, in an environment where food was scarce and energy expensive, an animal that grew enormous muscles without being able to find enough food to fuel them would not survive. These proteins were the body's way of keeping muscle growth in check and blocking this signal allows muscle to grow far beyond normal limits.

Monoclonal antibodies designed to bind and neutralize myostatin and/or activins have been in development for over two decades. The reason you haven't heard much about them is that until recently, their development pathway was focused almost entirely on rare diseases like spinal muscular atrophy, Duchenne muscular dystrophy, cancer-related cachexia, and other conditions characterized by severe muscle wasting. There was no commercial incentive, regulatory pathway, or cultural readiness to develop them for healthy adults seeking muscle optimization.

The GLP-1 disruption changed the equation in two ways. First, it created an urgent problem to solve - that GLP-1s can cause users to lose lean muscle mass along with fat. This is particularly concerning for older adults and those already prone to sarcopenia. Second, it generated enormous commercial and research momentum around health optimization as a category, making it plausible that muscle-gain drugs would be developed for broad use rather than just rare diseases.

As of early 2026, at least ten drugs targeting the myostatin/activin pathway are in clinical trials or entering clinical development. Regeneron's Phase 2 COURAGE trial, which is focused on combining semaglutide with trevogrumab (anti-myostatin) and garetosmab (anti-activin A), showed that this combination not only prevented the lean mass loss from semaglutide but shifted the composition of weight loss strongly toward fat. Apitegromab (originally designed for spinal muscular atrophy) completed Phase 3 trials and is expected to reach the US market in mid to late 2026. The field is advancing rapidly, and AI-powered drug discovery is accelerating the development of safer and more targeted versions.

Explore the evidence...

• Myostatin, Activin A, and Activin B are a family of related proteins that together act as a biological brake on muscle growth. They were only recently identified as targets for therapeutic intervention, which is why most people have never heard of them. Their discovery as a potential pathway for health optimization rather than just rare disease treatment is very recent.
  • Read about the science behind myostatin and activin blocking drugs and why they represent the next frontier in HOTs in our Rethinking Health report.
  • Explore the implications of stronger, leaner, more resilient populations for military readiness and national security.

• A significant drawback of GLP-1 drugs is that alongside fat loss they also cause loss of lean muscle mass. This is a meaningful clinical concern, particularly for older adults already at risk of sarcopenia. The Regeneron COURAGE trial directly addressed this problem, testing the combination of semaglutide with myostatin and activin blocking drugs. 
  
  • Read the Regeneron COURAGE trial results, which showed that combining semaglutide with myostatin and activin blocking drugs preserved lean mass while increasing fat loss.

• Some people use gyms, personal trainers, and fitness supplements for exactly the same reason some people use steroids — to build muscle and lose fat as effectively as possible. HOTs will soon offer a safer, legal, medically supervised path to those same goals, and that will have sweeping consequences for the fitness industry. Gyms, personal trainers, fitness equipment manufacturers, and supplement companies that have built their businesses around the difficulty of gaining muscle and losing fat will face the same disruption that the dieting industry faced when GLP-1s made weight loss genuinely easy. Demand will shift away from products and services used to "get fit" toward those used by "fit people".
  • Read about the full implications of HOTs for the fitness, sports, and recreation industries in our Rethinking Health report.

Witness the transformation

We are entering a new era of healthcare based on a categorically different kind of medicine whose purpose is not just to save us from illness, but to help us be the best version of ourselves.

The next generation of HOTs will trigger a multi-trillion-dollar global disruption, affecting dozens of industries across multiple sectors, driving a radical global improvement in health and wellness encompassing at least 1 billion people worldwide before 2040.

Optimizing well with advanced HOTs will soon become as important as eating well with nutritious foods. Nations, industries, and individuals that recognize this early and act decisively will be best positioned to capture the extraordinary benefits of this transformation.

Learn more about the HOT disruption and its implications for health, society, and the economy.

Disclaimer

The information provided in this FAQ is for general informational and educational purposes only and is not intended to constitute medical advice, diagnosis, or treatment. This content does not establish a doctor-patient relationship. The content regarding GLP-1 receptor agonists (or any other medical treatments) should not be used as a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or treatment options. Never disregard professional medical advice or delay in seeking it because of something you have read here. The authors and publishers of this FAQ and related report make no representation or warranty, express or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any information presented. Reliance on any information provided here is solely at your own risk.