Eli Lilly obesity pill maintains weight loss after Wegovy, Zepbound

Eli Lilly on Thursday said its closely watched obesity pill helped patients maintain the majority of their weight loss after they switched directly from taking the company’s injection Zepbound and Novo Nordisk’s rival shot Wegovy in a late-stage trial. 

The company also said it has filed for Food and Drug Administration approval of the daily GLP-1 pill, called orforglipron, for obesity. The FDA in November said it awarded a priority review voucher to that pill, which could expedite its review timeline to a few months. 

The positive trial data suggest that the pill could be an effective treatment for patients to transition to if they want to preserve their weight loss but don’t want to take weekly injections long-term. Many people who stop those shots regain much of the weight they initially shed. 

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 blockbuster GLP-1 market. But an oral pill for obesity from Novo Nordisk will likely enter the market first, giving the Danish drugmaker a head start in staking its claim in the 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 randomized to take either Eli Lilly’s pill or a placebo for another 52 weeks. The oral drug met the trial’s main goal of demonstrating superior weight loss maintenance compared to placebo, among people who previously experienced a plateau in their progress while taking the injections. 

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

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

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

While people in the Zepbound group appeared to regain more weight, the bigger focus is likely on those who transitioned from the drug’s top competitor, Wegovy. 

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

“Chipping away at the potential for Novo’s flagship product,” Seigerman wrote. 

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

Around 4.8% of people who switched to the pill from Wegovy discontinued treatment due to side effects, while 7.2% of those who switched to the oral drug from 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. 

No liver safety issues were observed, according to Eli Lilly. Full results on 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 in a similar way to Wegovy, Ozempic and Novo Nordisk’s diabetes pill Rybelsus, targeting a gut hormone called GLP-1 to suppress a person’s appetite and regulate blood sugar. Novo Nordisk is also seeking approval of an oral version of Wegovy for obesity, which could come by year-end.

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

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

They said they expect Eli Lilly’s pill to have a 60% share — or roughly $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 around $4 billion — of that segment.