In December 1921, Leonard Thompson was admitted to Toronto General Hospital so weak and emaciated that his father had to carry him inside. Thompson was barely a teenager, weighing all of 65 pounds, dying of diabetes. With so little to lose, he was an ideal candidate to be patient No. 1 for a trial of the pancreatic extract that would come to be called insulin.

The insulin did what today we know it can. “The boy became brighter, more active, looked better and said he felt stronger,” the team of Toronto researchers and physicians reported in March 1922 in The Canadian Medical Association Journal. The article documented their use of insulin on six more patients; it had seemingly reversed the disease in every case. As John Williams, a diabetes specialist in Rochester, New York, wrote of the first patient on whom he tried insulin later that year, “The restoration of this patient to his present state of health is an achievement difficult to record in temperate language. Certainly few recoveries from impending death more dramatic than this have ever been witnessed by a physician.”

Of all the wonder drugs in the history of medicine, insulin may be the closest parallel, in both function and purpose, to this century’s miracle of a metabolic drug: the GLP-1 agonist. Sold under now-familiar brand names including Ozempic, Wegovy, and Mounjaro, these new medications for diabetes and obesity have been hailed as a generational breakthrough that may one day stand with insulin therapy among “the greatest advances in the annals of chronic disease,” as The New Yorker put it in December.

But if that analogy is apt—and the correspondences are many—then a more complicated legacy for GLP-1 drugs could be in the works. Insulin, for its part, may have changed the world of medicine, but it also brought along a raft of profound, unintended consequences.