The arrival of semaglutide and similar GLP-1 drugs in recent years has ushered in a new era of obesity treatment. These drugs, which mimic the GLP-1 hormone, help people lose substantially more weight than they typically would with diet and exercise alone.
Semaglutide was developed by Novo Nordisk. It’s the active ingredient in the type 2 diabetes drug Ozempic and the obesity treatment Wegovy, both taken as a weekly shot. Though only Wegovy is approved for obesity, Ozempic has become the cultural shorthand for GLP-1 therapy (notably, Ozempic is often prescribed off-label for weight loss). But Ozempic’s reign on top looks to be coming to a close, if it isn’t already here.
Eli Lilly’s tirzepatide (Zepbound and Mounjaro) combines GLP-1 with a second hunger-related hormone called GIP and provides greater weight loss on average than semaglutide. And there’s a bevy of GLP-1-based drugs on the horizon vying for approval, with some likely to reach the public this year. Even Novo Nordisk is looking to upgrade its products. Last December, it won FDA approval for a once-daily pill form of Wegovy.
So here are some of the Ozempic rivals most likely to make a splash in the world of obesity treatment in the years to come.
1. Orforglipron
Developed by Eli Lilly, orforglipron mimics the GLP-1 hormone. Unlike most GLP-1 drugs, however, it’s taken as a once-daily pill.
In Phase III clinical trial data released last year, people on the highest dose of orforglipron lost, on average, 10% of their baseline body weight, compared to the 2.5% average weight loss seen in people taking a placebo. A study released last month also found that orforglipron could help people maintain most of the weight they lost on other GLP-1 drugs such as semaglutide or tirzepatide. Eli Lilly has since petitioned the FDA to approve orforglipron as an obesity treatment, with a decision expected sometime this spring.
Should it win approval, though, orforglipron will likely face some headwinds. The drug’s effectiveness might be below that of other popular drugs on the market, including Novo Nordisk’s oral version of Wegovy, approved late last year. But the company is banking on orforglipron having enough advantages to entice some doctors and patients.
For starters, many may prefer a daily pill over a weekly injection, either as a first-line treatment or as maintenance therapy. And unlike the Wegovy pill, orforglipron can be used without any food or timing restrictions (oral Wegovy needs to be taken in the morning on an empty stomach, at least 30 minutes before eating, to be most effective).
2. CagriSema
CagriSema is a weekly injectable drug being developed by Novo Nordisk. It combines the GLP-1 mimic semaglutide with cagrilintide, which mimics another hunger-related hormone called amylin.
In late-stage clinical trials, people taking CagriSema have lost up to 22.7% of their baseline weight over a year’s time. The company officially submitted the drug for FDA approval in late December, with a decision expected this year.
If approved, CagriSema could arguably become the most effective GLP-1 drug currently available to the public. It would also signify that amylin-based drugs could be another viable approach to obesity treatment. At the same time, the Phase III results weren’t quite as impressive as Novo Nordisk appeared to be expecting (25% or greater weight loss), and it will face stiff market competition from Eli Lilly’s existing drug tirzepatide, which has provided slightly lower but similar results in clinical trials.
3. VK2735
Eli Lilly and Novo Nordisk have dominated the landscape of GLP-1 therapy so far, but there are some competitors looking to challenge that dominance. For example, there’s Viking Therapeutics and its candidate VK2735. The drug combines GLP-1 and the hormone GIP (similar to tirzepatide) and is being developed in both an injectable and oral form.
In the latest Phase II data released last August, people taking oral VK2735 lost up to 12% of their body weight over a 13-week period. Typically, it takes about six months to a year for a GLP-1 drug to reach its peak effectiveness, indicating that VK2735’s ceiling hasn’t been reached yet. That said, the drug did have a relatively high dropout rate of 28%, with most related to gastrointestinal events like vomiting. Though GI symptoms are a common side effect of GLP-1 therapy, the discontinuation rate was higher than those seen with other GLP-1 drugs like semaglutide, so it’s at least something to keep an eye on.
The company is moving forward with its development of VK2735, having launched two Phase III trials last June.
4. MariTide
Another potential rival to Eli Lilly and Novo Nordisk might come from Amgen’s MariTide, short for maridebart cafraglutide.
MariTide has some intriguing differences compared to current drugs. It’s intended to be taken as an injection once a month, as opposed to the weekly injections required by current GLP-1s. The drug also takes a different chemical approach to treating obesity. While it still mimics GLP-1 activity, it also blocks the hormone GIP, in contrast to drugs like tirzepatide and VK2735, which mimic both GLP-1 and GIP.
So far, this alternate approach appears promising. In Phase II clinical trials, people with obesity have lost up to 20% of their weight over a year’s time while taking MariTide. People with type 2 diabetes also lost up to 17%, which is notable since people with diabetes typically lose substantially less weight on GLP-1 therapy than those without diabetes.
Amgen is currently conducting several Phase III trials of MariTide. Should it eventually win approval, the drug could offer a more convenient option for some potential users while also illustrating that there’s more than one way to treat obesity.
5. Retatrutide
Retatrutide is being developed by Eli Lilly, and it might be the most hyped experimental drug seen so far.
In clinical trial data released last month, people with obesity and knee osteoarthritis taking retatrutide lost up to 71 pounds over 68 weeks’ time, or nearly 30% of their baseline weight. Those results appear to be the most impressive documented for any weight loss drug to date and come close to matching the average effectiveness seen with traditional bariatric surgeries. Users also experienced a substantial reduction in knee pain.
Retatrutide’s effectiveness likely stems from it mimicking not one, not two, but three hormones that regulate our hunger and metabolism at once: GLP-1, GIP, and glucagon.
The drug probably isn’t going to be for everyone. Some people might simply not need or want to lose that much weight, and there is some early evidence that the drug’s side effects might be a bit more intolerable than drugs like semaglutide. Still, given the sheer potential effectiveness on display here, retatrutide could certainly become the next big thing in weight loss treatment.
Eli Lilly plans to release results from other Phase III studies of retatrutide in 2026, with an FDA approval likely not too far down the road.
6. Rejuva
Fractyl Health’s Rejuva isn’t as close to reaching the public as the other drugs mentioned so far. But it is the most futuristic-sounding option on the list.
It’s an injectable gene therapy designed to boost the body’s own production of GLP-1, possibly for life. Early studies in mice have suggested that a single course of Rejuva might be able to match the benefits seen with other GLP-1-based drugs. The company also argues that Rejuva could be easier to tolerate, since the therapy would really only stimulate added production in response to food, as opposed to the high circulating levels of GLP-1 induced by drugs.
The company is developing Rejuva for type 2 diabetes and obesity, with its obesity therapy intended to boost both GLP-1 and GIP production. It’s expected to start the first human trial of Rejuva, for people with poorly controlled diabetes, this year.
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