Ozempic 2.0 is on the way, and it could be even more transformative

Ozempic, and the class of weight loss drugs it has come to embody, has left its imprint seemingly everywhere: On the lives of millions of patients who’ve lost unprecedented amounts of weight. On grocery store shelves with new offerings explicitly catering to those taking the drugs. Even in the calculations of insurance companies studying the drugs’ effects on mortality. (Yes, there are Ozempic guides to Thanksgiving.)

For all the societal changes ushered in by GLP-1 drugs, their lofty price tags limit who can afford them. Many patients stop taking the medications after experiencing undesirable side effects. Others who could benefit have stayed on the sidelines because they don’t want to jab themselves.

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A new wave of the medicine is coming that could be even more transformative for human health: pills, more potent injectables and new compounds that might have fewer side effects or could be taken just once a month.

“With this newer generation of medications, we’re not just focusing on weight loss,” said David Lau, an endocrinologist and professor emeritus at the University of Calgary Cumming School of Medicine. “We’re talking about changes beyond what you see on the scale.”

Whether these next-generation treatments live up to that promise isn’t assured. They haven’t yet been approved by the Food and Drug Administration, which has warned consumers about unauthorized versions advertised on the internet. And it is common for the FDA to identify new risks after approving drugs, as it has done in recent years with the current GLP-1 blockbusters.

Such is the potential of these future offerings that Eli Lilly, by some measures the most dominant company in the weight loss field, reached a stock market value on Friday exceeding $1 trillion – the first company in the health care sector to hit that milestone.

Here is a look at what’s ahead, with analysis from obesity researchers who have led key clinical trials and who also have received fees from pharmaceutical companies related to their work.

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Next-generation pills

Novo Nordisk and Eli Lilly are both preparing to launch once-a-day weight loss pills by next year if the FDA approves them, as is widely expected. That would allow patients to avoid the jab of auto-injector pens with tiny needles.

“Some people are afraid of using needles and giving themselves injections,” Lau said.

Pills don’t require refrigeration – which adds cost and complexity to shipping and storing injectable medications – and there are signs that their price tags will be lower.

“What Henry Ford did with the car wasn’t to make a better car. He just made more of them and made them more accessible,” said Sean Wharton, a physician-researcher in Toronto and the lead author of two New England Journal of Medicine papers on oral GLP-1 drugs published in September. By offering more convenience at a lower cost, he said, these pills could do something similar for weight loss.

The trade-off is that pills being tested so far don’t work as well. In clinical trials stretching over a year, participants taking each drug have lost an average of about 11 to 14 percent of their body weight. That compares to about 15 to 20 percent weight loss for the most effective drugs given by injection.

Novo Nordisk’s Wegovy pill is likely to arrive for patients first. The company expects a decision from the FDA before the end of the year and could launch it in early 2026. Eli Lilly has cast its GLP-1 pill, orforglipron, as more convenient because it doesn’t have restrictions on eating and drinking.

Anticipation of the pills is so great that they are already included in drug price negotiations with the White House. Novo Nordisk and Eli Lilly struck deals with the Trump administration earlier this month to offer certain medications at a discount in exchange for access to Medicare, which until now has been prohibited from covering medications for weight loss. Novo Nordisk and Eli Lilly said they would offer the lowest dose of their new pills, if approved, directly to consumers for $150 a month.

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More weight loss, fewer side effects?

Today’s weight loss drugs work like keys that unlock the body’s natural processes, delivering instructions to produce more gut hormones that cue the brain when to stop eating. Existing drugs target one or two of these hormones. Eli Lilly is developing one that targets three, with the potential for even greater weight reductions.

Participants in a clinical trial who took the highest dose of this drug lost an average of 24.2 percent of their body weight over 48 weeks, according to a 2023 paper. Researchers expect the magnitude could be even greater over more time.

“There are patients who have severe obesity who will need stronger agents,” said Ania Jastreboff, director of the Yale Obesity Research Center and lead author of the 2023 paper. She is also co-writing with Oprah Winfrey a forthcoming book on obesity.

Before seeking FDA approval, Eli Lilly is awaiting results from multiple major clinical trials on the drug retatrutide, expected by the end of next year. Potential risks for some patients are that they could lose too much weight or muscle.

Drugmakers are also combining molecules known to suppress appetite in search of a more powerful effect. Novo Nordisk’s experimental drug CagriSema combines semaglutide, the active ingredient in Ozempic and Wegovy, with a compound that mimics another gut hormone called amylin. A clinical trial found that the combination boosted average weight loss to about 20 percent of body weight, or 5 percent more than semaglutide alone. The company expects to seek FDA approval for CagriSema next year. Eli Lilly earlier this month published data on a clinical trial for a drug that stimulates amylin.

“We’ve been studying amylin for weight loss for over 20 years,” said Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine. “In certain ways, it may be a better compound,” he said, adding that it appears to cause less loss of lean muscle and fewer stomach-related side effects.

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A monthly dose?

While many consider a daily pill to be more convenient than a weekly injection, drugmakers are closing in on another frontier: a drug that can deliver weight loss comparable to the best existing medications – that only needs to be injected once a month.

Earlier this month, Pfizer beat out Novo Nordisk in a bidding war to pay up to $10 billion for a biotech called Metsera, whose leading weight loss products are being studied for a once-monthly dose. Amgen’s experimental drug MariTide showed an average of up to 16 percent loss of body weight over a year, though trial data on side effects has raised concerns among analysts.

Jastreboff, the lead author of the MariTide study, said she envisions a future where “monthly or less frequent” injectables will be an option for patients.

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Will anyone be taking Ozempic in five years?

Eli Lilly’s tirzepatide-based drugs, Mounjaro and Zepbound, when combined have brought in roughly $25 billion through the first nine months of the year, making it the world’s top-selling medication. Novo Nordisk’s Ozempic and Wegovy aren’t far behind, at the equivalent of $23.5 billion over that time. But if patients can choose to take a weight loss pill, a more potent injectable or a drug with fewer side effects, what’s the appeal of the current blockbusters?

These medications could be enduring, researchers said. There is now years of data on the safety of GLP-1 drugs outside clinical trials. The FDA has approved Wegovy not just for weight loss but also reducing cardiovascular risk, while Zepbound is also an approved treatment for sleep apnea. It isn’t a sure bet that other medications that come along, however promising, will prove to have the same benefits.

“That is the hurdle that any other class is going to have to jump over to show that you can reduce the risk of heart attack, stroke and dying,” Aronne said.

A combination of market competition and government policy is also starting to bring down prices, which means that any new drug will have to be superior to justify a premium price over today’s GLP-1 drugs.

“Having more options also creates a space where there’s more competition,” said Jastreboff, hoping that this will lower costs and make the drugs more accessible.

Semaglutide, Wharton said, is “a really beautiful molecule” that could have long-term benefits for conditions like coronary artery disease and osteoarthritis. Reflecting on next-generation treatments, he offered a technology metaphor.

“Nobody is using the iPhone 1 anymore, right?” he said. “But at times, I wish I had my Blackberry back.”

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Video: What if the future of weight-loss drugs didn’t involve needles at all? Drugmakers are testing once-a-day pills and next-gen GLP-1 injectables that could be easier to use, cheaper to distribute and available to far more people. Reporter Daniel Gilbert explains what this could mean for patients.(c) 2025 , The Washington Post

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