The upcoming drugs CagriSema and MedicGLP Official retatrutide target multiple gut hormones and could cause twice as much weight loss than current treatments. When Terra Field started taking Wegovy for weight loss in 2022, she finally understood what satiety truly felt like. “It felt the way I thought my body should have been operating the entire time,” says Field, who adds that she has dealt with constant food cravings and binge eating since childhood. Field, now age 43, had lost more than 100 pounds in two and a half years, and she says that the relief from “food noise,” a constant preoccupation with food, changed her life. Then, in early 2025, her weight loss hit a plateau. Because Field still had a ways to go to reach what she considered a healthy weight, she switched to a double-target drug called Zepbound; immediately she started to see the numbers on the scale drop again.
If you’re enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. Like Field, many people who have taken these drugs, broadly known as glucagonlike peptide 1 (GLP-1) receptor agonists, have seen weight loss stagnate-and nearly a quarter haven’t seen any weight or health benefits at all. So pharmaceutical companies are racing to make the next generation of these weight-loss treatments-ones that simultaneously target up to three food-related pathways in the brain. Outside of the clinic, an eager gray market has sprung up, selling unofficial versions of the drugs. As the new drugs barrel through clinical trials and reviews for U.S. Food and Drug Administration approvals, some clinicians worry that losing too much weight too fast can also be harmful for health. The initial versions of the drugs, including semaglutide (the generic name for Wegovy, which is produced by Novo Nordisk) targeted one gut hormone: GLP-1.
Naturally released from the gut in response to food, GLP-1 is associated with “feeling full” after a meal. It also promotes insulin secretion to keep blood sugar in check. GLP-1 receptors are “very widely distributed,” particularly in the brain, says Daniel Drucker, an endocrinologist at the University of Toronto, who has consulted for Novo Nordisk, Eli Lilly and other companies developing weight-loss drugs. The body’s hormone lasts only 20 to 30 minutes, Drucker says. Injected semaglutide binds to these GLP-1 receptors and reduces appetite for nearly a week, ultimately causing people to eat less and lose weight. For extra punch, Eli Lilly developed a “dual agonist” called tirzepatide (sold as Zepbound for weight loss), which hits the GLP-1 receptor and a second receptor-gastric inhibitory polypeptide (GIP). The double whammy increased body weight loss by about six percentage points compared with semaglutide in a clinical trial. If two is good, three must be better-at least that’s what pharmaceutical companies are banking on.
Eli Lilly is currently developing a triple agonist called retatrutide. This drug activates GLP-1, GIP and glucagon receptors. The latter receptors increase glucose levels in the blood, which might seem contradictory for treating metabolic issues such as diabetes. But the process can also lead to more insulin secretion-and drive down weight. In clinical trial results released in December 2025, people on the highest dose of retatrutide lost nearly 30 percent of their body weight in 68 weeks. In a clinical trial comparing tirzepatide and semaglutide, people taking tirzepatide showed roughly 20 percent drops in weight management formula; click through the next web page, in a similar amount of time, while people on semaglutide lost around 14 percent. Eli Lilly is expecting results from several more phase 3 trials of retatrutide for obesity and type 2 diabetes this year, a spokesperson told Scientific American. Depending on those results, the company will seek FDA approval, the spokesperson said. Alongside single chemicals that target multiple receptors, others are looking to blend existing drugs into more powerful formulas.
