When Terra Field started taking Wegovi for weight loss in 2022, she finally understood what fulfillment really felt like.
“I felt like I thought my body was supposed to function all the time,” says Field, who says she has struggled with constant food cravings and binge eating since childhood.
Field, now 43, has lost more than 100 pounds in two and a half years, and she says the relief from “food noise,” a constant preoccupation with food, changed her life. Then, in early 2025, his weight began to decrease. Because Field still had a way to go to reach a healthy weight, he switched to a double-target drug called Zepbound; Immediately he began to see the numbers on the scale decreasing again.
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Like Fields, many people who have taken these drugs, known broadly as glucagonlike peptide 1 (GLP-1) receptor agonists, have seen plateaued weight loss — and about a quarter have seen no weight or health benefits. So pharmaceutical companies are racing to create the next generation of these weight-loss treatments—ones that simultaneously target three food-related pathways in the brain. Outside the clinic, a curious man Gray market selling unofficial versions of medicines has emerged. As new drugs undergo clinical trials and reviews for U.S. Food and Drug Administration approval, some physicians worry that losing too much weight too quickly could also be harmful to health.
triple Threat
Early versions of drugs, including semaglutide (generic name for Vegovy, manufactured by Novo Nordisk), targeted a gut hormone: GLP-1. Released naturally from the gut in response to food, GLP-1 is linked to the “feeling of fullness” after a meal. It also promotes insulin secretion to keep blood sugar under control. GLP-1 receptors are “very widely distributed,” especially 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.
Drucker says the body’s hormones only last for 20 to 30 minutes. Injected semaglutide binds to these GLP-1 receptors and reduces appetite for about a week, ultimately causing people to eat less and lose weight.
For added punch, Eli Lilly developed a “dual agonist” called tirazeptide (sold as Zepbound for weight loss), which hits the GLP-1 receptor and a second receptor—gastric inhibitory polypeptide (GIP). Body weight started decreasing due to double blow about six percentage points Compared with semaglutide in a clinical trial.
If two is good, three should be better—at least that’s what pharmaceutical companies are counting on. Eli Lilly is currently developing a triple agonist called retretutide. This drug activates GLP-1, GIP and glucagon receptors. The latter receptors increase glucose levels in the blood, which may seem counterintuitive for treating metabolic issues like diabetes. But this process can also lead to more insulin secretion – and weight loss. “When you combine (the three goals) together, it certainly improves diabetes control and certainly reduces the person’s body weight,” says Drucker.
In clinical trial results released in December 2025, people taking the highest dose of rettrutide lost about 30 percent of their body weight over 68 weeks. In a clinical trial comparing tirazepitide and semaglutide, people taking tirazepitide saw a weight loss of about 20 percent over the same time, while people taking semaglutide lost about 14 percent.
Eli Lilly is expecting results from several more Phase 3 trials of retretutide for obesity and type 2 diabetes this year, a spokeswoman said. scientific American. Based on those results, the company will seek FDA approval, the spokesperson said.
drug cocktail
Others are looking to combine existing drugs into more powerful formulas, with single chemicals targeting multiple receptors. On December 18, 2025, Novo Nordisk applied for FDA approval of a two-drug combination called Cagrisema. In the name, “Sema” stands for semaglutide, while “cagri” refers to cagrilintide, a peptide drug that locks onto amylin receptors. amylin Another hormone that promotes satiety and slows gastric emptying. Drucker says that similar to GLP-1 receptors, amylin receptors are also in areas of the brain related to hunger, and stimulating them sends the message that you’re not hungry. But amylin receptors and GLP-1 receptors occur in slightly different groups of brain cells. “Activating those two pathways will help you lose more weight than one drug alone,” he says.
Jesse Richards, M.D., an internal medicine and obesity physician at the University of Oklahoma School of Community Medicine, says cagrilintide may also reduce some of the common gastrointestinal side effects of GLP-1 drugs, such as severe nausea and vomiting. (Richards gives paid talks for Novo Nordisk and Eli Lilly.) Many GLP-1 receptors are scattered in the postrema area of the brain, which “induces most of your nausea,” Richards explains, while amylin receptors are on a slightly different pathway that corresponds to less nausea.
In trials, participants taking Caigrisema lost about 23 percent of their body weight at 68 weeks. A representative of Novo Nordisk said scientific American The company expects to see FDA review in 2026.
Too much of a good thing?
Pharmaceutical companies make a lot of money from these drugs. The latest results from Eli Lilly’s rettrutide trials helped the company take a hit. $1-trillion stock price. The upcoming wave of drugs may also help people who do not respond well to existing GLP-1 drugs.
“People differ in underlying biology and appetite regulation, and some people are unable to reach or maintain higher doses (of existing medications) because of side effects,” says Arisha Moise, a clinical epidemiologist at the Lady Davis Institute for Medical Research in Quebec.
Newer drugs may be better tolerated, but scientists and doctors are cautious about their rapid weight-loss effects – for example, retatrutide can reduce someone’s weight by one-third in less than a year. Such a huge drop in weight can be dangerous. “Large-scale weight loss increases the risk of gallstones, no matter how it occurs, and there is an increasing focus on losing muscle as well as fat,” says Moise. “With medications that are too strong, some people may lose too much weight and become underweight. And in older adults, rapid weight loss may also cause low blood pressure and dizziness.”
For Field, who is still reacting to Zepbound, the drug’s advances have been both life-changing and life-saving. If she hits another plateau or if the food cravings return, Fields says, she’ll try a new, souped-up version of these medications. But she says she tries to “be fat-positive” and hopes other people will feel empowered to make their own decisions about their body size, especially as weight stigma remains an issue in society as well as the medical community.
The rise of highly effective weight loss drugs has also raised some important—and thorny—ethical questions. Drug prices remain sky-high, and insurance coverage may be limited or denied altogether. Over the next five years, as these advanced drugs enter the market, Richards predicts that people and their doctors will effectively be able to “choose” to be the weight they want — and “that’s a scary concept.”
