The long history of underground drug use abounds with secret societies—colorful cliques of like-minded individuals surreptitiously experimenting with newfangled compounds in an effort to understand their mysteries.
Mid-19th-century France saw artists and intellectuals like Baudelaire and Dumas gathered at the Club of the Hash Eaters to partake of the powerful sticky cannabis concentrate. In the latter half of the 20th century, Dow chemist Alexander Shulgin, famous for popularizing MDMA and a range of other potent psychedelic analogues, held gatherings at his home, sampling his latest creations with a group of like-minded fellow travelers. And earlier this year, when 48-year-old Jake Terry wanted to test the effects of retatrutide, a new but not-yet-approved compound developed by the pharmaceutical giant Eli Lilly, he bought some online and took it to his friends.
Unlike Shulgin or Baudelaire’s experiments, retatrutide is not psychoactive. It’s a weight-loss injectable, like semaglutide (marketed as Wegovy) or tirzepatide (marketed as Zepbound). But the key difference with this weight-loss drug, besides the pesky matter of its legality, is that it appears to be much, much more powerful than those approved so far. On the back of phase II trials, it’s already being hailed as a game-changer.
Retatrutide works by the same means as its predecessors, by interacting with receptors that are central to the body’s metabolism, ultimately lowering people’s appetite and slowing digestion. But where semaglutide acts on one receptor (the glucagon-like peptide-1, or GLP-1, receptor), and tirzepatide on two (GLP-1 and the gastric inhibitory polypeptide, or GIP, receptors), retatrutide has been nicknamed “Triple G” for its ability to work on three hormone receptors (those for GLP-1 and GIP, as well as the glucagon, or GCG, receptor).
“These are three chemically related but distinct receptors that have their own distinct biology,” says Richard DiMarchi, professor of chemistry and chair in biomolecular sciences at Indiana University. “With the three together … you can actually make a single molecule, like a master key, that opens multiple doors as effectively as [individual] keys, and achieve superior outcomes.” DiMarchi knows these drugs well, having conducted pioneering research on this class of chemicals as far back as the late 1990s while employed at Eli Lilly as group vice president of research and development. (He left the company in 2003, in part because he felt the company didn’t then prioritize obesity treatments or see the benefit of an injectable weight-loss drug.)