There is a new anabolic drug expected to get approval for sale in the United States in the near future. However, before I go any further I must point out that none of the published research or marketing literature regarding this drug compound mention muscle building (anabolism). Only reversal of muscle atrophy (wasting) is discussed. The drug is being indicated for the prevention of muscle loss due to aging (sarcopenia) and chronic catabolic conditions such as kidney disease. Another quite interesting application for this drug involves a clever drug combination, and this is also in the FDA approval pipeline, I will discuss that later on in the article. Bottom line here is let’s not fool ourselves - this drug is a muscle builder and I will bet the farm that it will be “abused” as such by athletes / bodybuilders in the near future
BGE-105/Azelaprag
The experimental drug has been designated the code name BGE-105 and it was developed by a company called BioAge Labs. BioAge Labs is a company that does research on development for drugs that help combat aging and health complications related to the aging process. This company develops drugs and conducts the clinical research on drugs to gain FDA approval, however they do not market drugs once approved - Big Pharma companies fulfill that role.
BGE-105 has been given a generic drug name, and that name is Azelaprag. Azelaprag is an orally active analog of the naturally occurring small peptide Apelin. Apelin is a myokine, which means it is a signaling molecule produced in muscle. More specifically it is an exerkine, meaning it is a signaling molecule produced in the muscle in response to exercise. Apelin works in both an autocrine fashion (binding and activating cell membrane bound Apelin receptors on muscle cells) as well as in a paracrine fashion (binding and activating Apelin receptors in other tissues, including and not limited to cardiac, vascular, gastrointestinal, and brain tissues).
Action in Muscle
Activation of Apelin receptors in muscle cells increases proliferation of muscle satellite cells. Muscle satellite cells are key players in muscle growth (hypertrophy) and they function as donators of new myonuclei to existing muscle cells, resulting in increased gene expression related to the synthesis of muscle contractile proteins.
Apelin is normally released in skeletal muscle in response to exercise, and it contributes to the repair and regrowth of muscle tissue post exercise. Apelin, manufactured synthetically by recombinant DNA technology, has been administered to mammals and it has been shown to prevent and reverse muscle wasting due to aging and disease. This makes Apelin a promising treatment for maintenance and growth of muscle tissue, unfortunately being a peptide hormone it must be regularly administered by injection which is not a preferred route for patient compliance. Thankfully, BioAge Labs was able to develop a non peptidyl small chemical agonist for the Apelin receptor, and this compound they called Azelaprag. Azelaprag is orally active, making it an attractive drug candidate and approval is being sought for the treatment of sarcopenia, kidney disease related muscle loss, and maybe other applications as well. However, the most interesting application of Azelaprag involves its combination with a very popular drug, and it is this combination that has put Azelaprag on the map.
Tirzepatide/Azelaprag
Tirzepatide, sold under the trade name Mounjaro, belongs to a class of drugs known as Glucagon-Like Receptor-1 Agonists (GLP-1 agonists). These drugs were originally developed to help treat diabetes, as they have been shown to reduce levels of glycated hemoglobin (A1C), which is the most accurate test to determine chronic metabolic damage due to elevated blood sugar levels. GLP-1 agonists were soon shown to be extremely effective weight loss agents since they dramatically decrease appetite amongst other things. It was not long until drugs in the class were being remarketed as treatments for obesity. Semaglutide (Ozempic) was the first, and soon afterwards Eli Lilly marketed its licensed GLP-1 agonist Mounjaro for the same purpose.
GLP-1 agonists were a breakthrough in obesity treatment as no other obesity drugs ever came close to delivering the dramatic weight loss that they could. There is one problem with GLP-1 agonist promoted weight loss though, and that is the fact that roughly half of the pounds lost are in the form of muscle protein. This is not the healthiest of things, nor is it an optimally desired outcome cosmetically speaking. BioAge Labs recognized this issue, and decided to investigate the combination of its drug Azelaprag with the GLP-1 agonist Tirzepatide for weight loss. Results were very promising as not only did the subjects lose even more weight than with Tirzepatide alone, the weight loss observed was almost exclusively in the form of fat tissue. No serious side effects were seen.
Conclusion
A new orally active muscle building (or sparing) drug has been developed by a company called BioAge Labs. BioAge Labs has teamed up with Eli Lilly and a drug combination of Azelaprag with the GLP-1 agonist Tirzepatide is now being tested in humans for weight loss with the sparing of lean body mass. If this combination gets approval then it could be a huge breakthrough in medically assisted healthy weight loss.