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In the race to find Ozempic 2.0, a few stand-outs are emerging.
While GLP-1 drugs have paved the way for a new era of healthcare, they have some drawbacks. They need to be injected (a draw-back for some patients), that injection must be administered once a week for effects to last, and manufacturers struggled to keep up with demand.
Competition is on the way: Dozens of experimental new weight-loss medications are in development as biotech companies race to get a slice of a market forecast to be worth $100 billion.
Some are combining multiple hormones at once for enhanced effects to regulate appetite, blood sugar, and digestion. Some are trying to package these sought-after ingredients into pill form, or injectables that last longer.
The next breakthrough drug may not be available until at least 2027, but the leading candidates in production give a good sense of what this market could look like in years to come.
"Anti-obesity medications are emerging at an astonishing pace," Dr. Christopher McGowan, a gastroenterologist and obesity medicine specialist, told Business Insider. "Forthcoming medications take the blockbuster GLP-1 medications and up the ante."
Why it's interesting: Retatrutide is a next-gen medication that acts on three different hormones, earning it the nickname Triple-G.
That means it could lead to more weight loss than current medications like Ozempic, Wegovy, and Mounjaro, comparable to bariatric surgery.
How it works: Eli Lilly's retatrutide drug is administered the same way as the market leaders Ozempic, Wegovy, Mounjaro, and Zepbound: it's a once-weekly injection.
What's unique is the substance.
Like semaglutide (the active ingredient in Ozempic and Wegovy), it works on GLP-1, a hormone that regulates blood sugar and appetite.
Like tirzepatide (the drug in Mounjaro and Zepbound), it also works on GIP, a hormone that manages blood sugar.
Uniquely, retatrutide has an additional effect, mimicking another hormone called glucagon, which may help increase the body's energy use. The idea is that it promotes weight loss by not only curbing appetite, but also burning more calories.
Current research: The results of mid-stage trials found that patients taking retatrutide lost an average of 58 pounds in 11 months, more and faster weight loss than has been seen with drugs currently on the market.
Timeline: Retatrutide is currently being studied in Phase III trials which are scheduled to be completed in early 2026.
Why it's interesting: Early research suggests VK2735, from California-based Viking Therapeutics, could work faster than competitors like semaglutide and tirzepatide.
How it works: VK2735 acts on both GLP-1 and GIP, similar to tirzepatide (the active ingredient in Mounjaro and Zepbound).
It's being tested in pill form as well as a once-weekly injection.
Current research: A mid-stage trial found patients on VK2735 lost an average of 14.7% of their body weight (about 32 pounds) by 13 weeks.
It hasn't been directly tested against other medications but the results are comparable to what we've seen in trials of semaglutide (Ozempic, Wegovy) after 68 weeks. That suggests similar weight loss but in a fraction of the time.
Timeline: Viking Therapeutics recently announced it would meet with the FDA about the end of Phase II for VK2735 injections before 2025. The oral form of VK2735 is expected to enter Phase II trials by the end of this year, too.
Why it's interesting: Eli Lilly may beat Viking Therapeutics to get the first oral GLP-1 to market.
Their drug orforglipron appeals to patients who can't or don't want to use injected medications. It is also expected to be cheaper, since it's easier to produce (orforglipron isn't a peptide like other GLP-1 drugs).
However, the clock is ticking.
Novo Nordisk already has an oral semaglutide to treat type 2 diabetes, sold under the brand name Rybelsus, and they're trialing a high-dose version of that pill that could be approved for weight loss.
How it works: The active ingredient in the daily pill is a small molecule which slow digestions and manages blood sugar and insulin, similar to semaglutide (Ozempic, Wegovy).
Current research: Results from Phase II trials found that people taking orforglipron lost between 9.4% and 14.7% of their body weight, on average, in 36 weeks.
Timeline: Current late-stage trials are expected to last into 2027.
Why it's interesting: CagriSema is a once-weekly injection that combines semaglutide (active ingredient in Ozempic and Wegovy) with a compound targeting another hormone, cagrilintide.
This combination is expected to help people lose significantly more weight than semaglutide alone, Novo Nordisk says.
How it works: Cagrilintide mimics the effects of a naturally-occurring hormone to regulate appetite and digestion and lower blood sugar. CagriSema adds it to the already-popular drug semaglutide, which itself helps manage hunger and blood sugar levels.
Novo's chief financial officer said in an earnings call that it would source cagrilintide from a third-party company, which could help with manufacturing. Supply issues and shortages have previously hampered its semaglutide products.
Current research: One early study found patients lost more weight on CagriSema (about 15% weight loss over 32 weeks) than either semaglutide or cagrilintide alone.
A Novo Nordisk executive told Reuters that projections from the data suggest it could help people lose even more, up to 25% of their weight, over a longer timeline.
Timeline: Phase III clinical trials for Cagrisema are ongoing and slated to last until late 2025. The drug could be available in 2026.
Why it's interesting: MariTide, from biotech company Amgen, could be a much longer-lasting treatment than current drugs. It only needs to be injected once a month — or even less frequently — compared to the once-weekly requirement for semaglutide and tirzepatide.
"Longer-acting versions of GLP-1 medications offer the potential for greater convenience and potentially improved adherence and sustained use over time," McGowan said.
The catch is whether side effects might last longer, too.
How it works: MariTide is similar to Mounjaro and Zepbound because it mimics GLP-1 and GIP hormones.
The difference is that MariTide dials down GIP receptor activity. Amgen says this makes it easier for the body to burn fat.
"This is fascinating because it appears that both enhancing and opposing the GIP receptor influence weight regulation, which speaks to how little is still known about the actual weight-regulating mechanism of certain gut hormones," McGowan said.
Current research: Patients in a small early-stage study lost 14.5% of body weight on average in 12 weeks. Those who got just a single dose lost an average 8.2% of their body weight.
Timeline: Data from Phase II trials is expected later this year, and planning is underway for Phase III trials.
