New GLP-1 weight-loss drugs are coming—and they’re stronger than Wegovy and Zepbound

When Terra Field started taking Wegovy for weight loss in 2022, she finally understood what satiety actually felt like.

“I was feeling the way I thought my body should have been functioning all the time,” says Field, who adds that she has dealt with constant food cravings and binge eating since childhood.

Field, now 43, lost more than 100 pounds in two and a half years, and she says relief from “food noise,” a constant preoccupation with food, changed her life. Then, in early 2025, his weight loss plateaued. Because Field still had a way to go to reach what she considered a healthy weight, she opted for a dual-target drug called Zepbound; Immediately, she began to see the numbers on the scale drop again.

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Like Field, many people who took these medications, widely known as glucagonlike peptide 1 (GLP-1) receptor agonists, saw their weight loss stall and nearly a quarter saw no weight or health benefits. So pharmaceutical companies are racing to create the next generation of these weight loss treatments, which simultaneously target up to three diet-related pathways in the brain. Outside the clinic, a gray market has emerged, selling unofficial versions of the drugs. As new drugs undergo clinical trials and reviews to gain approval from the U.S. Food and Drug Administration, some clinicians worry that losing too much weight too quickly could also be harmful to health.

Triple Threat

Initial versions of the drugs, including semaglutide (the generic name for Wegovy, produced by Novo Nordisk), targeted an intestinal hormone: GLP-1. Naturally released by the intestine in response to food, GLP-1 is associated with a “feeling of fullness” after a meal. It also promotes insulin secretion to control blood sugar levels. 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 only lasts 20 to 30 minutes, Drucker says. Injected semaglutide binds to these GLP-1 receptors and reduces appetite for almost a week, causing people to eat less and lose weight.

For added 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 to 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 medication activates the GLP-1, GIP and glucagon receptors. These latter receptors increase blood glucose levels, which may seem contradictory for treating metabolic problems like diabetes. But the process can also lead to greater insulin secretion and weight loss. “When you add [the three targets] together, this definitely improves diabetes control and definitely brings the person to a lower body weight,” says Drucker.

In clinical trial results released in December 2025, people receiving the highest dose of retatrutide lost almost 30% of their body weight over 68 weeks. In a clinical trial comparing tirzepatide and semaglutide, people taking tirzepatide experienced about 20 percent weight loss in a similar amount of time, while people taking semaglutide lost about 14 percent.

Eli Lilly expects results this year from several more Phase 3 trials of retatrutide for the treatment of obesity and type 2 diabetes, a spokesperson said. Scientific American. Based on these results, the company will seek FDA approval, the spokesperson said.

Drug cocktails

Alongside single chemicals targeting multiple receptors, others are seeking to blend existing drugs into more potent formulations. On December 18, 2025, Novo Nordisk requested FDA approval for a two-drug combination called CagriSema. In the name, “Sema” means semaglutide, while “Cagri” refers to cagrilintide, a peptide drug that binds to amylin receptors. Amylin is another hormone that promotes satiety and slows gastric emptying. Similar to GLP-1 receptors, amylin receptors are also found in areas of the brain related to appetite, and stimulating them sends messages that you’re not hungry, says Drucker. But amylin receptors and GLP-1 receptors are found on slightly different groups of brain cells. “Activating both of these pathways will help you lose more weight than just one drug,” he says.

Cagrilintide might also alleviate some of the common gastrointestinal side effects of GLP-1 drugs, such as severe nausea and vomiting, says Jesse Richards, an internal medicine and obesity clinician at the University of Oklahoma School of Community Medicine. (Richards gives paid speaking engagements for Novo Nordisk and Eli Lilly.) Many GLP-1 receptors are scattered throughout the area postrema of the brain, which “is what causes most of your nausea,” says Richards, while amylin receptors occur on a slightly different pathway that corresponds to less nausea.

In trials, participants taking CagriSema lost about 23 percent of their body weight in 68 weeks. A Novo Nordisk representative said Scientific American which the company hopes to see the FDA review in 2026.

Too many good things?

Pharmaceutical companies could make a lot of money from these drugs. The latest results from Eli Lilly’s retatrutide trials have helped the company reach a stock market value of $1 trillion. The coming wave of drugs could also help people who have not responded well to existing GLP-1 drugs.

“People differ in the underlying biology and regulation of appetite, and some are unable to achieve or maintain higher doses. [of current drugs] because of the side effects,” explains Areesha Moiz, clinical epidemiologist at the Lady Davis Institute for Medical Research in Quebec.

The new drugs may be better tolerated, but scientists and clinicians are wary of their intense effects on weight loss: Retatrutide can reduce a person’s weight by a third in less than a year, for example. Such extreme weight drops can be dangerous. “Significant weight loss increases the risk of gallstones, regardless of how it is achieved, and there is increasing attention to losing muscle along with fat,” Moiz says. “With very strong medications, some people can lose too much and lose weight. And in older people, rapid weight loss can also contribute to low blood pressure and dizziness.”

For Field, who still responds to Zepbound, advances in medications have both changed and saved lives. If she hits another plateau or the food noise returns, Field said, she would try a new, improved version of these medications. But she adds that she tries “to be fat positive” and hopes that others will feel empowered to make their own decisions about their size, especially when weight stigma remains an issue in society as well as the medical community.

The rise of hypereffective weight-loss drugs has also raised important – and thorny – ethical questions. Drug prices remain exorbitant and insurance coverage may be limited or even denied altogether. Over the next five years, as these advanced drugs enter the market, Richards predicts that people and their doctors could effectively “pick” the exact weight they want — and “that’s a scary concept.”