Eli Lilly's Anti-Obesity Pill Maintains Weight Loss After Wegovy, Zepbound

Eli Lilly Thursday said its closely followed anti-obesity pill helped patients maintain most of their weight loss after they stopped taking the company's Zepbound shot directly and NordiskThe rival shot Wegovy at a late stage in the trial.

The company also said it has asked the Food and Drug Administration to approve the daily GLP-1 pill, called orforglipron, for obesity. In November, the FDA said it had granted a priority review voucher to that pill, which could speed up its review timeline to a few months.

Eli Lilly shares rose more than 2% on Thursday following the announcement.

The positive data from the trial suggest that the pill could be an effective treatment for patients to transition to if they want to preserve their weight loss but do not want to receive weekly injections long-term. Many people who stop these injections regain much of the weight they initially lost.

While Eli Lilly's pill appears to cause less weight loss overall than existing injections, Thursday's results highlight its potential role as a needle-free maintenance treatment in the successful GLP-1 market. But an oral obesity pill from Novo Nordisk is likely to hit the market first, giving the Danish drugmaker a leg up to bet in this space.

The phase three trial followed more than 300 patients with obesity who previously took Wegovy or Zepbound for 72 weeks in a separate late-stage study. Those people were then randomly assigned to take the Eli Lilly pill or a placebo for another 52 weeks. The oral drug met the trial's primary goal of demonstrating superior maintenance of weight loss compared with a placebo, among people who previously experienced a plateau in their progress while taking the injections.

On average, patients who switched to Novo Nordisk's Wegovy pill only regained about 2 pounds of the weight they had initially lost by the end of the trial. Meanwhile, on average, people who switched to the Zepbound pill only regained about 11 pounds of the weight they had initially lost at the end of the study.

That means people in the Wegovy group kept about 95% of their weight loss after the switch, while those in the Zepbound group kept about 80%.

“Obesity is a chronic, progressive disease, and maintaining weight loss remains a significant challenge for many,” Kenneth Custer, president of Lilly Cardiometabolic Health, said in a statement.

He said the trial showed that the pill “helped people maintain the weight they worked so hard to lose” and that, if approved, it could “provide a convenient alternative for millions of people living with obesity around the world to continue their long-term health journey.”

While people in the Zepbound group appeared to regain more weight, the most attention is likely to be focused on those who transitioned from the drug's main competitor, Wegovy.

In an October note, BMO Capital Markets analyst Evan Seigerman said positive trial results could give Eli Lilly “a unique opportunity to capture some of the revenue” from chronic treatment with semaglutide, the active ingredient in Novo Nordisk's Wegovy and diabetes injection Ozempic.

“Cutting the potential of Novo's flagship product,” Seigerman wrote.

In a note Thursday, Leerink Partners analyst David Risinger said the data “will help drive commercial success and consensus expectations” for Eli Lilly's pill. He said the firm expects the drug to generate $2 billion in sales by the end of 2026, $9 billion by the end of 2027 and $16 billion by the end of 2028.

Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women's Hospital, said the results “remain excellent” even though patients regained some of the weight they lost.

But he said that “for this to be a good change, these orals are going to have to be less expensive for insurance companies to cover than injectables, right?” Anti-obesity shots currently have list prices of about $1,000 a month before insurance, although both Eli Lilly and Novo Nordisk have lowered the direct-to-consumer prices of their drugs for cash-paying patients.

It's unclear how the companies will price their respective pills. But under recent deals with President Donald Trump, the companies said initial doses of their upcoming oral medications, pending approval, will cost $149 a month for anyone who gets them through the TrumpRx direct-to-consumer website. That site launches in January.

The overall safety and tolerability (or how well patients manage treatment) of the pill were consistent with previous late-stage studies. The most common side effects were related to the gastrointestinal tract and were generally mild to moderate in severity.

About 4.8% of people who switched to the Wegovy pill stopped treatment due to side effects, while 7.2% of those who switched to the oral drug Zepbound did the same. Meanwhile, those rates were 7.6% and 6.3% among patients who switched to a placebo from Wegovy and Zepbound, respectively.

According to Eli Lilly, no liver safety concerns were observed. Full results from the trial, called ATTAIN-MAINTAIN, will be presented at an upcoming medical meeting and published in a peer-reviewed journal next year.

Eli Lilly's pill works similarly to the Rybelsus diabetes pill from Wegovy, Ozempic and Novo Nordisk, targeting a gut hormone called GLP-1 to suppress a person's appetite and regulate blood sugar. Novo Nordisk is also seeking approval for an oral version of Wegovy for obesity, which could arrive by the end of the year.

But unlike those three treatments, Eli Lilly's pill is not a peptide drug. That means it is more easily absorbed by the body and does not require dietary restrictions like oral Rybelsus or Wegovy do.

In an August note, Goldman Sachs analysts forecast that pills will capture a 24% share (or about $22 billion) of the global weight-loss drug market in 2030, which they expect to be worth $95 billion in total.

They said they expect Eli Lilly's pill to have a 60% share (or about $13.6 billion) of the daily oral segment of the market in 2030. They expect Novo Nordisk's oral semaglutide to have a 21% share (or about $4 billion) of that segment.