Eli Lilly to release weight loss pill orforglipron trial data

Patients, doctors and investors will soon learn a lot more about a new, more convenient treatment that could shake up the booming weight loss drug market.

Eli Lilly plans to release initial results from several late-stage clinical trials on its experimental once-daily obesity pill, orforglipron, this year. The company has said it expects to unveil data from five studies in patients with Type 2 diabetes and two trials in people with obesity in 2025. 

Analysts expect the pill to be as effective, safe and tolerable to take as Novo Nordisk‘s semaglutide – the active ingredient in its popular but costly weight loss injection Wegovy and diabetes drug Ozempic. The trial results are among the pharmaceutical industry’s most critical and closely watched of the year, as they bring Eli Lilly’s drug one step closer to becoming a new, needle-free alternative for weight loss and diabetes. 

“This could join a growing toolbox of medications for obesity, and it could be a game-changer,” said Dr. Eduardo Grunvald, medical director for UC San Diego’s Center for Advanced Weight Management.

If it enters the market, orforglipron could help more patients access the treatments and alleviate the supply shortfalls of the injections on the market. The pill could also help Eli Lilly solidify its dominance in the growing segment as a slate of other drugmakers race to bring a product to the market.

Offering the first oral version of a so-called GLP-1 could help Eli Lilly capture an even greater share of the market for that popular class of weight loss and diabetes drugs. Eli Lilly is currently about three years ahead of other drugmakers developing pills, including Pfizer, AstraZeneca, Roche, Structure Therapeutics and Viking Therapeutics, Guggenheim analyst Seamus Fernandez told CNBC.

Some analysts expect the market for GLP-1s to be worth more than $150 billion annually by the early 2030s. Oral GLP-1s could grow to be worth $50 billion of that total, Fernandez said. 

In a statement, Eli Lilly said it is “investigating orforglipron for the potential to bring a safe and effective treatment to people with these diseases who are looking for a convenient, oral option.”

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. 

But unlike those three medications, Eli Lilly’s pill is not a peptide medication. That means it is absorbed more easily in the body and doesn’t require dietary restrictions like Rybelsus does. 

It is unclear whether orforglipron will have a hefty list price similar to those of the injections, which cost roughly $1,000 per month, or whether it will help expand insurance coverage for obesity treatments. Medicare and many employer-based plans still don’t cover those drugs. But so-called small molecule pills will at least be easier for Eli Lilly to manufacture than injections. 

In January, Eli Lilly CEO Dave Ricks said the pill could receive U.S. regulatory approval as soon as early 2026. The company also said in its annual report in February it recorded a nearly $550 million “pre-launch inventory” charge for oforglipron, meaning it is preparing to manufacture the drug even before its approval. 

“That’s a good indicator that they are comfortable with what they’re seeing across the trials,” BMO Capital Markets analyst Evan Seigerman told CNBC.

Eli Lilly has benefitted from the windfall from tirzepatide – the active ingredient in its weight loss injection Zepbound and diabetes shot Mounjaro –  which targets GLP-1 but also activates another gut hormone called GIP.

Fueled by those treatments, Eli Lilly has become the largest global pharmaceutical and health-care company by market cap, with a market value of about $814 billion as of Monday. The company raked in more than $45 billion in revenue in 2024 alone, a significant share of which came from its portfolio of diabetes and obesity products.

Patients can inject Zepbound and Wegovy under their skin with a click of a button, but must follow specific instructions, such as storing the shots at certain temperatures and injecting in a different spot each week. Meanwhile, Rybelsus must be taken in the morning on an empty stomach with no more than four ounces of plain water.

Orforglipron does not have dietary restrictions, and will also offer an option for patients who could benefit from treatment but are afraid of needles. 

Th pill could also tap into new markets in countries that don’t have the resources for the cold supply chains needed to store and administer GLP-1 injections, Guggenheim’s Fernandez said.

People who lost weight on the injections and are tired of taking a shot every week could also be “good candidates” to switch to a pill and take them as maintenance doses, which are meant to be taken long term to prolong the effects of a drug, Seigerman added. Eli Lilly is studying orforglipron as a maintenance dose in patients who took tirzepatide throughout a phase three trial called SURMOUNT-5, with results expected in early 2026. 

Still, some patients who don’t mind taking injections may continue their current treatment regimen, UCSD’s Grunvald noted. He said some people already take several pills for other conditions each day, so they may prefer to take an injection once a week “and forget about it rather than adding another pill.”

Eli Lilly’s pill could also be more fit for people who are overweight or “modestly obese,” said Leerink Partners analyst David Risinger. Those who have a very high body mass index will “best be treated with injectables that offer greater efficacy,” Risinger said.

While orforglipron is expected to be as good for weight loss as Wegovy, Zepbound, on average, is more effective at helping patients lose weight than Novo Nordisk’s injection, according to real-world data and a head-to-head trial on the drugs.

A pill is a welcome alternative for patients like Willow Baillies, 29, who has been injecting herself with cheaper, compounded versions of Zepbound because her insurance does not cover the branded medication. 

The Food and Drug Administration, in most cases, now bars compounding pharmacies from making those unapproved versions because it declared the Zepbound shortage over in December. 

Baillies, a human resources specialist based in Milwaukee, Wisconsin, said a pill would “offer peace of mind because I don’t have to think much about taking it.” Currently, her injections require careful preparation, such as disinfecting her entire counter with alcohol pads. 

Orforglipron’s entrance into the market could also help the weight loss drug market reach more patients in the primary care setting who are not currently receiving treatment but could benefit from it, Seigerman said. While some primary care doctors can and do prescribe GLP-1s, others are hesitant due to concerns about side effects and administration since they are injections.  

He said the primary care part of the market is key for the weight loss drug market to hit Wall Street’s lofty forecasts.

He said he doesn’t expect orforglipron to cost significantly less than existing injections because pharmaceutical products are “typically priced by the value that they bring, regardless of the route of administration.” For example, Rybelsus costs about $997 a month before insurance, the same list price as Ozempic. 

Risinger said he expects orforglipron to be priced at a slight discount to Zepbound, which means Eli Lilly’s pill could cost significantly less than Wegovy. 

The list price of Wegovy – nearly $1,350 per month – is already around a 20% premium to Zepbound’s list price of just under $1,100 per month, he said. That means if the pill costs 10% to 15% less than Zepbound, it would be almost a 30% to 35% discount compared to Wegovy, according to Risinger. 

But Risinger said he does not necessarily expect the pill to lead to better insurance coverage for obesity medications. He believes orforglipron will be covered by some plans like Zepbound is, but certain employers will likely still fear that some patients are only using obesity drugs for cosmetic purposes. Other employers are still balking at the high costs associated with covering those treatments. 

Jill Skala, a teacher in western Pennsylvania, said she would “definitely consider” taking a pill if it was less expensive than Zepbound and had “equal efficacy or better.” Skala, 49 is currently taking Zepbound and also has a nine-month supply of compounded tirzepatide, which she expects to use until the end of the year. 

“I would probably just stay with Zepbound if [the pill] wasn’t significantly less expensive, as long as Zepbound was still working for me,” Skala told CNBC.

Overweight or obese patients who took 36 milligrams of the pill once a day lost 13.5% of their body weight on average after 36 weeks in Eli Lilly’s phase two trial. That compares with an average weight loss of 2.3% for people who received a placebo.

Eli Lilly expects weight loss in people with diabetes to be “significantly less” than patients with obesity who don’t have diabetes, the company’s Chief Scientific Officer Daniel Skovronsky said on an earnings call in February. That’s based on prior studies on orforglipron and other GLP-1 therapies, he noted. 

Schott said weight loss among diabetes patients could come in between 6% to 8%. He also expects hemoglobin A1c – a blood test that measures the average blood sugar level over the past two to three months – to improve by 1.8 to 2.1 points. That would be in line with results seen in diabetes patients who took Ozempic. 

In a phase two trial, orforglipron led to an HbA1c reduction of up to 2.1% at 26 weeks in adults with diabetes, compared to a decrease of 0.4% among those who took a placebo. 

However, how well patients tolerate Eli Lilly’s pill – specifically the rate of gastrointestinal side effects in the trial – will be the “key focus” of the phase three study results, according to Schott. It’s an issue top of mind for doctors, patients and investors because side effects such as nausea and vomiting are a significant reason why some people stop taking the injections.

Schott said the bar for orforglipron is nausea rates of less than 25% and vomiting rates in the low double digits for diabetes patients. 

He expects orforglipron to cause slightly worse rates of gastrointestinal side effects in patients with obesity. That could lead to “tolerability worse than Zepbound but closer to Wegovy,” Schott added.

Orforglipron’s nausea and vomiting rates in the phase two trial were “meaningfully greater” than those among patients who took 2-milligram doses of semaglutide in a phase three trial, Leerink’s Risinger said. 

But he expects patients to tolerate Eli Lilly’s pill better in phase three trials because they are longer in duration than the mid-stage studies and likely involve slower titration. That refers to how quickly patients start at a lower dose of a drug and ramp up to a higher target dose. 

On safety, Schott said he expects a “very low probability” of any issues that could put the entire development program for orforglipron at risk. He also believes it is highly unlikely that there will be any concerns related to liver toxicity – an issue that derailed one of Pfizer’s experimental obesity pills.