By Peter Loftus

An intriguing new option is coming for weight-loss drugs: a pill that you take once a day to shed pounds, rather than the weekly injections that have powered the anti-obesity revolution up to now.

The rationale: Some people don't like needles and view pills as more convenient. And pills will be easier and less expensive for drugmakers to manufacture compared with more complex injectables. That might make them cheaper than the popular Wegovy and Zepbound shots.

"A lot of patients have tried different agents that either didn't work for them, or they had side effects and they want to try something new," said Dr. Scott Isaacs, an obesity-medicine specialist in the Atlanta area and president of the American Association of Clinical Endocrinology. "To have another option to switch to, I think, is going to be appealing for a lot of people."

Novo Nordisk's pill version of semaglutide -- the main ingredient of both Wegovy and diabetes treatment Ozempic -- is positioned to become the first GLP-1 pill approved specifically for weight loss. The company has applied for U.S. Food and Drug Administration approval, and a decision is expected by the end of the year, setting up a potential launch by early 2026.

Eli Lilly's offering has a new main ingredient, orforglipron, which works differently than the main component of its injectable Zepbound, tirzepatide. Orforglipron is a GLP-1 drug, which mimics a gut hormone to help suppress appetite. But it doesn't also mimic a second gut hormone, the way Zepbound does, which likely explains why studies suggest it is less effective than the injectable. The company plans to apply for FDA approval by the end of the year, setting up a potential launch sometime during 2026.

Other companies including AstraZeneca and Structure Therapeutics are developing pills that could arrive in a few years if testing is successful.

These new pills could have trade-offs versus the shots. You might not lose as much weight, studies have shown. And the pills might cause gut-related side effects such as nausea in more patients compared with the injectables. Doctors and analysts say the pills might be more suitable for people who need to lose a more-modest amount of weight, while people with severe obesity may need to stick with the injectables.

Even with their limitations, the market for GLP-1 weight-loss pills could be big. They could eventually make up about 25% of the total market, estimates David Risinger, an analyst at Leerink Partners, which focuses on healthcare investment banking. "They still have the potential to generate mega-blockbuster sales because consumer demand for oral obesity pills will be tremendous," Risinger said.

The current crop of injected drugs is expected to generate about $72 billion in sales globally this year, including their use in diabetes, according to analyst firm TD Cowen.

The companies may have to overcome skepticism from doctors, said TD Cowen analyst Michael Nedelcovych. His surveys indicate that doctors generally view the injectable drugs as more effective, and don't see a burning demand from patients for pills. But if pricing is lower for the pills, insurance coverage may be better, which could help their sales, he said.

The injectables carry list prices of more than $1,000 a month and discounted cash prices of roughly $500 a month. High costs have been a big reason why many insurance plans in the U.S. don't cover weight-loss drugs.

Lilly and Novo Nordisk haven't disclosed specific pricing plans for their pills, but some analysts expect them to be priced at a discount to the injectables.

The leading weekly injected medicines, Novo Nordisk's Wegovy and Lilly's Zepbound, have been highly effective at helping people lose significant weight. Zepbound's highest dose has been shown to help people lose an average of more than 22% of their body weight after more than a year of treatment, while Wegovy can help people lose about 17%.

Yet their manufacturers have struggled to make enough to meet demand, partly because of limited manufacturing capacity for the complex task of making sterile injectable drugs packaged in an auto-injector device. Making pills is less complex, and there is more global capacity. And, pills don't require cold-chain distribution and storage, while the injectables need to be kept refrigerated.

Drugmakers see pills as an important way to get GLP-1s to more people.

"You're getting the weight loss, the glucose control, all of those things that are really important, in a way that looks very much like injectable GLP-1's," said Kenneth Custer, president of Lilly's cardiometabolic health unit. "But you're getting it now in a pill format that can really be deployed at scale and is easy for patients to use."

Novo Nordisk already sells a semaglutide pill called Rybelsus for Type 2 diabetes. The semaglutide pill it developed for weight loss comes in a higher dose. In a Phase 3 study of more than 300 people, the pill version of Wegovy helped people lose 16.6% of their body weight after 64 weeks of treatment, Novo Nordisk said. Some patients experienced gut side effects that are common for GLP-1 drugs, such as nausea and vomiting. About 7% of patients discontinued treatment because of side effects.

Novo Nordisk may be constrained in how much of its new weight-loss pill it can manufacture because it must cram a lot of the main ingredient into each pill to ensure each person absorbs enough by ingestion, analysts have noted. That is because, like injected semaglutide, the pill is made up of peptides, which are larger than the small molecules that pills are traditionally made of.

Nevertheless, the pill is a similar size to Rybelsus, so the issue is more of a challenge to the company's manufacturing efforts than for patients.

The Novo Nordisk pill also must be taken on an empty stomach and then the patient is supposed to wait 30 minutes before eating. Some analysts view this as a disadvantage to Lilly's pill, which has no such restriction.

Novo Nordisk Chief Scientific Officer Martin Holst Lange said the company has a strong production setup and is prepared for a full product launch if it is approved. He doesn't see the requirement for taking the pill on an empty stomach being a major limitation for the weight-loss version, noting that its Rybelsus pill also has that requirement.

Novo Nordisk this month announced plans to reduce its global workforce by about 11%. The company said major projects including the weight-loss pill are continuing.

Lilly took a different approach than Novo Nordisk. The main ingredient for its GLP-1 pill, orforglipron, is a small molecule, meaning the pills can be manufactured in a more traditional way.

Orforglipron has delivered more modest weight loss in studies than Zepbound or Wegovy, however. In one study of more than 3,100 people who didn't have diabetes, people taking the highest dose of orforglipron for more than a year lost 12.4% of their body weight, on average.

Another concern was that about 10% of patients taking the highest dose of orforglipron stopped treatment early because of side effects such as nausea and vomiting.

But Lilly said the results are sufficient for orforglipron to be an appealing alternative to injections. Lilly expects orforglipron to be a viable starting treatment for many people with excess weight. It is also studying the possibility that patients who lose weight on injectable drugs could switch to Lilly's pill to keep the weight off.

Write to Peter Loftus at Peter.Loftus@wsj.com

(END) Dow Jones Newswires

September 18, 2025 10:00 ET (14:00 GMT)

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