- Eli Lilly makes the popular shots Mounjaro and Zepbound.
- Next, the company says they have a pill coming that could be as powerful as rival Ozempic.
- The company’s head of obesity said the ultimate goal is to develop a once-per-year shot.
Imagine this: You walk into your doctor and get your yearly flu vaccine and a yearly dose of your weight-loss injection. If Eli Lilly has its way, this may be the future of obesity care.
Eli Lilly makes some of the most powerful weight-loss drugs in the world. The company has pivoted dramatically over the past several years, going from a major insulin provider to a GLP-1 injection juggernaut.
Leading the charge is Patrik Jonsson, a 35-year Lilly veteran who got his start as a sales rep for the company in Sweden. For the past year, Jonsson has run Lilly Diabetes and Obesity, which means he oversees everything from insulin shots to the newer, high-demand drugs now known as “weight-loss” shots: Mounjaro, prescribed for diabetes, and Zepbound, for obesity.
If you ask him what he’s most excited about, it’s not a daily, weekly, or even monthly medicine for weight loss or diabetes control. His eye is trained on a one-and-done solution, a slow-release compound that patients could one day have access to at an annual checkup and then not have to worry about for a year. Jonsson says scientists inside the company are already working on making a yearly weight-loss shot a reality.
Here are the small steps they’re taking this year to get there.
Eli Lilly’s oral weight loss pill, orforglipron
Eli Lilly competitor Novo Nordisk kicked off the weight-loss drug craze when it started selling Ozempic in the US in 2017. Back then, the once-weekly drug was only approved to treat type 2 diabetes.
It took a while to become popular as an off-label weight loss aid. Once it did, demand skyrocketed above what the company could produce.
In clinical trials, Ozempic has consistently helped people lose, on average, about 15% of their body weight over the course of a year. Still, it requires a special injector pen and consistent refrigeration. Patients also reported uncomfortable side effects from Ozempic, like nausea, vomiting, and diarrhea.
Eli Lilly hopes that a new pill it’s developing can do everything Ozempic can without the hassles. It’s called orforglipron (put the emphasis on the second syllable: or-FOUR-glip-ron).
“It takes a while to get used to it, even for us,” Jonsson said of the awkward generic drug name.
Like Ozempic, the new pill is designed to mimic the glucagon-like peptide 1 hormone that our bodies produce naturally, albeit in very small, transient doses. In earlier phase two trials the company sponsored, patients taking orforglipron achieved about 14.7% weight loss, on average, almost matching Ozempic.
“When you do phase three trials, you continue for a longer period of time, and normally you see a continued weight loss,” he said.
The company is working on wrapping up those final phase three trials right now. The hope is that results will be available for regulators to review by the end of 2025.
“We actually believe that we have an oral here that could generate the same amount of weight loss as you see with Wegovy or Ozempic, but in a pill,” Jonsson added, echoing what Eli Lilly CEO Dave Ricks said during the JPMorgan Healthcare Conference earlier this month.
If that final trial goes well, orforglipron could be available to consumers (with a snappier, yet-to-be-decided brand name) in early 2026. That would be good news for folks with needle phobia, but the even bigger opportunity would be the mass market that a daily weight-loss pill could unlock.
“Most importantly, when you look at the global need, we expect that there are more than one billion people across the globe that are suffering from obesity,” Jonsson said. “There is no way that we can meet those demands with injectable treatments today.”
Novo Nordisk already has a daily oral GLP-1 pill with the same active ingredient as Ozempic. Called Rybelsus, it has been FDA-approved to help treat type 2 diabetes since 2019. It isn’t approved for weight loss, and in trials of patients with diabetes, it wasn’t as effective as Ozempic or Mounjaro at decreasing “food noise” or prompting weight loss.
Rybelsus can also be kind of a chore to take, because it works best when patients fast overnight beforehand and then only drink a few small sips of water for the first 30 minutes afterward. Jonsson says orforglipron is likely more effective than Rybelsus because of pharmaceutical differences between the molecules, which impact things like absorption.
“This has been an evolution, to discover incretins with more appealing pharmacological properties,” he said. “Not all GLP-1s are the same.”
Retatrutide, the ‘King Kong’ drug to mimic bariatric surgery
Eli Lilly isn’t pivoting away from weekly weight loss injections entirely. It’s also working on another, even more powerful weight-loss shot.
While Ozempic mimics one hunger-relieving hormone, and Mounjaro mimics two, Eli Lilly is working on what’s called a “triple agonist,” with three different hormone-like substances inside.
Researchers testing the drug say this shot could be as powerful as bariatric surgery, with patients losing roughly a quarter of their body weight in one year.
“You have GLP-1 receptor agonist, you have GIP receptor agonist, but then we’re adding the pharmacology of glucagon as well,” Jonsson said. (Glucagon, like insulin, is one of the hormones that regulates blood sugar.)
The shot, called retatrutide, is already looking more powerful than any drug on the market in this category, earning it the nickname “King Kong” from doctors and researchers working in diabetes and weight loss treatment. It will likely be reserved to treat patients who have a BMI over 35.
“We also expect there to be some benefits in terms of cardiovascular benefits, kidney benefits, and liver benefits because it has demonstrated reduced liver fat in earlier studies,’ Jonsson said. “So it could potentially be really, really appealing for the treatment of MASH [a chronic liver disease], for example.”
While it’s still uncertain whether final retatrutide trial results will be available to submit to the FDA in 2025, Jonsson said it “might” happen, setting up the drug to potentially become available in 2026.
If the “King Kong” shot does become available, that might be enough horsepower to treat the most severe obesity cases. Then, instead of chasing more and more powerful injections, the diabetes and weight loss market may pivot to perfecting techniques, aiming to reduce side effects or lower muscle loss while upping fat loss, Jonsson said.
“With adding the pharmacology of glucagon, we might get very close to the amount of weight loss one should aspire to,” he said.
The dream: a once-a-year obesity shot
When Jonsson goes into full crystal ball-gazing mode, he imagines a future where these drugs could become as convenient as flu vaccines — though affordable weight-loss medications may remain a pipe dream.
“Really, the big aspiration here would be to find something once and done,” he said.
He imagines a futuristic scenario in which patients are administered their once-yearly hormone shot during an annual doctor’s visit.
“That’s what I know our researchers are aspiring to deliver, but it’s not going to happen this decade,” he said.
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