The first truly revolutionary oral drug for obesity, made by Eli Lilly, may soon be on the way
In an hour-long meeting at Eli Lilly and Company’s headquarters in Indianapolis on April 15, the pharmaceutical company’s top executives met, like they had dozens of times before, to hear the long-awaited results of a study involving a new drug.
There’s always a lot riding on these presentations, called readouts. But this one, for Lilly’s first diabetes and weight-loss pill based on the GLP-1 hormone, was particularly fraught. Days before, rival pharma giant Pfizer had announced it was abandoning its oral weight-loss drug after worrying side effects involving liver problems were reported in one participant in the trial. It was the second drug in its class that had failed for Pfizer.
So, David Ricks, Lilly’s CEO, was understandably cautious. It was the latest in a string of milestone moments for the understated leader of the country’s most dynamic pharmaceutical company. Lilly executives took TIME inside the complex process of developing the new pill that unfolded over a series of conversations and a visit to the company’s headquarters and labs in Indianapolis to detail both the scientific advancements as well as the unique culture at the pharma giant that made the drug possible. And now it all came down to this meeting. Early phase studies had been promising, but anything can happen when a new drug is tested on thousands more people.
“In my job as CEO, I’ve walked into a room like that about 30 times, and most of them have been for successful drugs—but there have been failures,” he says. “You can kind of tell by the way people are sitting what the outcome is going to be. But what you don’t know is the degree.”
Buy a copy of The Big Promise cover here
The body language was encouraging. And the data, outlined in about 50 slides shown to Ricks and his team over the course of the hour, was clear: The pill, called orforglipron, was a success.
For the diabetes patients in the study, taking the drug daily lowered their A1C—a measure of their blood sugar—and helped them lose weight at slightly lower rates as Lilly’s injectable drug in the same category, tirzepatide (known as Mounjaro). Tirzepatide targets two weight-related hormones while orforglipron only targets one, so the fact that orforglipron came close was impressive. But it wasn’t until Ricks saw the slide comparing the side effects experienced by those on the drug vs. those receiving placebo that he was truly reassured. There were no liver issues recorded, and the side effects, such as diarrhea, nausea, vomiting, and constipation, were similar to those linked to tirzepatide. “When that slide came up, I was like, ‘OK, we have a drug,’” says Ricks.
Orforglipron still has more hurdles to clear before the U.S. Food and Drug Administration (FDA) decides whether to approve it. And while establishing the benefits among people with diabetes is a critical first step, Lilly is conducting further studies. This summer, Ricks expects to sit through a few more meetings like this one, when his team will see results from studies testing the drug as a weight-loss treatment in people who are overweight or obese but don’t have diabetes. Still, these first findings are exciting and reassuring, Ricks says, since the drug appears safe, and people with diabetes tend to lose less weight on these types of medications than people without diabetes.
If orforglipron is eventually approved by federal regulators, it would become the first GLP-1 oral drug for weight loss to hit the market. While Novo Nordisk currently makes an oral GLP-1 drug, it’s only approved for diabetes; it also uses a lower dose than orforglipron and produces about half the weight loss on average. Orforglipron comes with no food or drinking restrictions, while people have to take Novo’s drug 30 minutes before eating or drinking, and must limit their consumption of fatty, spicy, and sweet foods.
The implications—if Lilly’s drug makes it through the testing and review process—could be transformative, not just for the company, but for patients.
The promise and excitement around orforglipron stems from what doctors have learned about popular injectable medicines—Mounjaro, Zepbound, Ozempic, and Wegovy—that target a group of hormones known as incretins, which include GLP-1. They are potent ways to treat diabetes and obesity, yes, but they’ve also helped reduce the risk of heart disease, sleep apnea, and other chronic conditions associated with weight, including kidney and liver diseases. Even beyond chronic conditions, there is encouraging evidence that they may help to address addiction—because of the way they affect satiety and reward centers in the brain—and even Alzheimer’s, thanks to their anti-inflammatory features. (These are not benign medications for everyone who takes them, however, and have been linked to many side effects ranging from mild to severe, from gastrointestinal issues to blood clots, an eye disease, hair loss, and more.)
As a pill, orforglipron would be cheaper to make and reach more people than its injectable predecessors, since it wouldn’t require refrigeration to store or special injector pens to use.
“We can think about its use in disease beyond Type 2 diabetes and obesity,” says Dr. Dan Skovronsky, Lilly’s chief scientific officer, “where patients typically want an oral medicine. We’re testing it for hypertension, for example.” An oral medicine that’s more effective than current treatments could transform the way obesity is managed, potentially even preventing people who are on the verge of diabetes or obesity from developing the diseases at all by helping them control their blood sugar or weight with a daily pill. As doctors and patients start relying on these new treatments, a drug like orforglipron may play a role in helping people to maintain weight loss, which remains challenging.
“After people have lost weight, maybe by using an injectable, could they stay on an oral [medicine] to maintain their weight?” says Skovronsky. “These are the kinds of ideas we’re thinking about for how an oral medication might fit in on broad population uses.”
All of this could unlock a huge financial windfall for Lilly. The market for injectable anti-obesity drugs, currently dominated by Zepbound (made by Lilly) and Wegovy (from Novo Nordisk), is expected to grow to $100 billion in sales by 2030. A pill would expand this market in significant ways, and potentially dominate it, by reaching people in parts of the world where an injectable drug that has to be refrigerated is simply out of reach.
A more accessible way to manage weight—and the myriad chronic conditions linked to obesity—could transform not just the health care system as more people potentially avoid the heart, liver, and kidney diseases that currently account for much of the health care burden worldwide, but also the processed food and diet industries that have fueled and capitalized on the obesity epidemic. Because the medications are so effective in curbing appetite, demand for high-calorie and sweetened foods and beverages is already dipping in some instances, and significant shifts in what people eat, and how much they consume, are likely to follow.
Most drug companies are lucky to have one breakthrough or blockbuster drug at a time. Lilly has two (and counting). In July 2024, it received FDA approval for Kisunla, an Alzheimer’s treatment that reduces symptoms of cognitive decline more dramatically than any other drug. It also announced encouraging early results in 2024 from its new gene therapy, which helped a deaf boy hear again. All of this has made Lilly, at nearly 150 years old, the most valuable drug company in the world and potentially on its way to becoming the first trillion-dollar health-care company.
Since Ricks became CEO in 2017, the company’s market capitalization, a reflection of the value of the company’s stock, has soared to nearly $700 billion—nearly double that of the next-most valuable pharma company, Johnson & Johnson. Yet Ricks is not exactly the ruthless corporate titan you might expect to lead such an aggressive drive to make history. More mild-mannered than take-charge showman, Ricks prefers to take an under-the-radar approach to dominating the industry.
He regularly grabs lunch at the company cafeteria, and when he is, as he describes it, “flummoxed” about something, “I go talk to people on the ground. I’ve got a big job, and they know who I am. These are hourly workers, but they’re not impressed by me. They’re basically like, ‘Fix this, it’s frustrating.’ They’ll tell you what’s wrong.”
And Ricks finds a way to fix it fast—an approach that has earned him admirers among fellow CEOs.
When Ricks joined Lilly right out of business school in 1996, he never imagined he’d one day run it. His fiancée—now wife—was in medical school at Indiana University, and he just needed a job. “It was a necessity in a way,” he says of his first job at the company. Roles in sales, marketing, and overseeing operations in the U.S. and abroad led him to the top job in 2017.
By the time he became CEO, Lilly was already known for launching the first human insulin in 1982—which was also the first recombinant drug of any kind approved by the FDA—along with other diabetes treatments and blockbuster drugs in other disease areas, like Prozac for depression in 1987.
Concerned that Lilly was perhaps getting too complacent from its past success, in his first speech as CEO to 150 company executives, he emphasized three things Lilly needed to prioritize in order to maintain its leading role in the pharmaceutical world: speed, an openness to looking outside its four walls to enrich its pipeline, and teamwork. “We’re seeking to be the fastest-moving large pharma company, which I think we basically are, but now we’re trying to beat our own benchmarks,” he says. Orforglipron was developed in six years, which is 30% to 40% faster than any competitor, Ricks says.
He has brought a greater willingness to acquire and bring in outside experts and ideas—something Lilly historically liked to keep in house. Former board members saw Lilly’s focus on building internal expertise for specific diseases as a double-edged sword: while it gave the company in-depth knowledge that could streamline drug development strategies, it was also insular and limiting when it came to ensuring Lilly had access to the most innovative strategies. “We often, at our worst, were pretty satisfied,” Ricks says of the company’s culture. “We’re here in Indianapolis—we’re the anchor tenant of the city and state, and we’re the largest employer. Pretty much if you live here and work at Lilly, all your neighbors think you’re awesome. And so you think you’re awesome. But sometimes you are, and sometimes you’re not. Improvement starts by re-basing what your assumptions are about what ‘good’ is.”
Finding new ways to control blood sugar was the perfect test case. “When I arrived, there was a moment to go beyond insulin,” says Ricks. In the early 2000s, Lilly partnered with biotech Amylin Pharmaceuticals to develop the first-in-class drugs that would eventually lead to Mounjaro. “It was a big step, although the drug needed to be improved a lot to be as useful as the ones we have today,” says Ricks.
The potential was obvious. So was the drive. “If it’s going to be a great drug,” Ricks told his leadership team, “let’s make sure it says Lilly on it.”
Orforglipron was just such a drug. By 2018, Ricks also had a comrade-in-arms in Skovronsky, who had joined the company after Lilly acquired his biotech company in 2010. Like Ricks, Skovronsky wasn’t shy about questioning the inertia that often plagues a big company like Lilly. At a meeting discussing drug development timelines, in which it was clear that Lilly fell shy of industry benchmarks, “I kind of spoke up and said, ‘If I understand correctly, our goal is to be below average?’” says Skovronsky.
Like Ricks, he was eager to ensure that the company didn’t miss important opportunities because they weren’t looking for them—opportunities such as orforglipron. The drug was developed by the Japanese pharmaceutical company Chugai, which had found a way to put some of the weight-loss features of the incretins into an oral form that wouldn’t lose all its potency and get chewed up by the acids in the stomach and digestive system. Compelled by the early data, Ricks decided in 2018 to license the development and commercialization of the drug. That was just a year after Ozempic, Novo Nordisk’s diabetes drug, was approved by the FDA and four years before Lilly’s first incretin-based diabetes treatment, Mounjaro, was launched. There was no way to predict then that these drugs would go on to transform the treatment of diabetes and obesity. “If [orforglipron] is successful, it will go down as probably the best business development deal in the history of pharma,” says Ricks of that early decision. “And our team went out and found it.”
However, the promising molecule required double the number of steps to build than typical small-molecule medications. It had only been made in small quantities for early testing in animals and a small number of people. Sarah O’Keeffe, senior vice president of product development and research, remembers the marching orders from her managers: “‘Sarah and team, you go figure out how to do that quickly,’” she says.
O’Keeffe and her team were accustomed to building drugs that required maybe a dozen steps. Orforglipron required 30. Using Ricks’ north star of speed, and nudged by increasing competition in the field, O’Keeffe and her team took a risk and proposed an entirely new manufacturing process—one that would prioritize efficiency and environmental safety by using fewer solvents and producing less waste. She and her team tweaked the process they had used to mass produce tirzepatide, a peptide, to now make a small molecule, orgforglipron, which they hadn’t done before.
They created a mini version of the manufacturing process and invited Ricks to the lab to explain the new approach and get his approval to build it to scale. “They had this little skunk works kind of thing and said it was seven times more efficient,” he says. Within days, he greenlit the switch to the riskier, but potentially more efficient manufacturing process. “That decision, and that process…is a big part of our success now,” he says. “We would be backlogged for years if we were just using the old process.”
Encouraging such enterprise didn’t happen overnight. Ricks faced a problem that’s likely unique to a company founded and grounded in the heartland of the Midwest: people at the company were too nice and too respectful of one another—to the point that they would rarely contradict or argue in meetings. “Lilly nice,” as it’s known in the company, was actually dampening creativity since there was little incentive to risk raising alternative views at meetings.
Ricks had to introduce conflict and contrary opinions in meetings to induce richer discussion and honest evaluation of projects and their risks and benefits. He encouraged teams to assign a devil’s advocate to argue a dissenting view and present a case for going against the conventional wisdom or majority opinion. Ricks has his own devil’s advocates on his board and on his management team; he turns to them when making critical decisions about whether to invest billions of dollars, for example, to take a promising drug into late-stage human trials. “They’re one-way doors,” he says of the expensive studies. “You can only start. You cannot stop once you begin these studies, so you better set them up the right way, and you better be sure about the ones you advance.”
While Lilly has been satisfactorily answering to its shareholders in recent years, rewarding them with about $34 billion in annual revenue, it and other pharmaceutical companies are increasingly having to answer to a public that is demanding broader access to medicines at lower prices. In response, Ricks launched Lilly Direct in 2024, turning Lilly into the first pharmaceutical company to offer its products, including tirzepatide, directly to consumers—and for those paying out of pocket, at a slightly lower cost. “It was about taking out intermediaries,” says Ricks of the usual way that prescription drugs move from manufacturers like Lilly, through large distributors and pharmacy benefit managers who maintain formularies and set the prices patients see, to pharmacies. “There’s a lot of dialogue about middlemen in health care, and we said, ‘OK, let’s just skip all that.’ For people who don’t have insurance, what can we do? We can have a lower price point. And we can offer it directly to them.”
About 100,000 people purchase Zepbound for weight loss through Lilly Direct each month, which represents about 10% of the people using the drug. For many patients, it’s a cheaper, easier alternative to the traditional pharmacy route. And it’s setting a precedent for how patients may soon be getting their prescription drugs; in March, Novo Nordisk announced its NovoCare Pharmacy, which also provides its weight-loss medication directly to consumers.
For Ricks, it was the logical next step after being the first company to drop prices of insulin to $35 a month out of pocket for patients. The two decisions build on the Lilly 30×30 program that was launched the year before he became CEO, which aims to provide its drugs to 30 million people each year by 2030. “Why didn’t these things happen earlier? I don’t know, but I think people feel constrained by norms, and we just pushed beyond them. Do what you do well, where you can, and push the boundary where that’s not enough.”
Companies like Lilly may only be able to push those boundaries so far, especially when it comes to regulatory decisions and economic pressures such as the tariffs the Trump Administration is planning to levy on imports. Pharmaceuticals have been exempt from the first round of tariffs, but on April 14, the Administration began investigating potential taxes on pharmaceuticals as well as the ingredients used to make them. While some of the materials required to make orforglipron come from Europe, Ricks says that in five years, he anticipates that all of the GLP-1-based drugs for the U.S. market will be manufactured domestically. “We are planning for global introduction of orforglipron, and we’re ramping up new factories to come online to support that global use,” he says. He’s invested nearly $50 billion since 2020 in expanding and building four new Lilly manufacturing facilities in the U.S., including in North Carolina, Wisconsin, and Indianapolis. The Indianapolis facility includes a manufacturing plant that will begin producing drugs in 2026 and a site that represents the largest investment to make active pharmaceutical ingredients for synthetic medicines in the country’s history. Lilly will also announce three more such sites in the U.S. this year.
“The key thing is to direct our research intensity not where the market is today, but where the problem is today,” Ricks says. For orforglipron, that meant taking a risk on a tricky compound with big ambitions—and, he hopes, being proven right.
Correction, April 17
The original version of this story misspelled Sarah O’Keeffe’s last name. It is O’Keeffe, not O’Keefe.