If it seems like new medications for weight loss are coming out at a rapid rate, it’s because they are. The first GLP-1 oral pill became available earlier this year. Now, a new oral GLP-1 from drug company Eli Lilly—called Foundayo (orforglipron)—just got FDA approval.
Wajahat Mehal, M.D., Medical Director of the Yale Center for Weight Management, says even more options are likely on the way. Retatrutide, a so-called “triple agonist” is said to be on the horizon as soon as this year, too. In fact, Dr. Mehal believes that, eventually, there will be more than 15 different drugs for treating obesity. Some are also exploring mimicking the natural hormone amylin, which is involved in extending the time it takes for food to leave the stomach.
How is the new pill different? Here’s what to know about Foundayo.
How Orforglipron Fits Into the GLP-1 Landscape
First, a quick lay of the land. There are two peptides for weight loss currently in circulation: There’s semaglutide (Ozempic, Wegovy) which activates the glucagon-like peptide-1 (GLP-1) receptor. Tirzepatide (Zepbound, Mounjaro) activates that same receptor as well as another one called GIP (glucose-dependent insulinotropic polypeptide), making it slightly more effective for weight loss. Retatrutide, which isn’t yet approved, activates those two and a third. Until early this year, all of these only came in weekly injections.
The Wegovy pill came out in January which made it the first oral GLP-1 formulation. Like the Wegovvy injection, it’s still semaglutide, and is roughly as effective in the oral formulation as it is as an injectable (so, still less effective than tirzepatide, broadly speaking).
What makes Foundayo unique is that it’s not actually a peptide at all, but the first “small molecule” weight loss drug, explains Dr. Mehal. “I think conceptually it’s a huge breakthrough.” Consumers will appreciate that this new pill may be even easier to use than the Wegovy pill, as it doesn’t come with food or drink restrictions (more on that later).
While a peptide is an organic, biological compound (like a cheese or meat), a small molecule is essentially chemicals, which are more stable and easier and cheaper to make, Dr. Mehal says.
How Effective Is the New Pill?
Clinical trials suggest the new oral pill, orforglipron, will be comparable in effectiveness to oral semaglutide (the Wegovy pill). Specifically, of the patients who took the largest dose—36 milligrams—of orforglipron for 72 weeks, 54.6 percent had a weight reduction of 10 percent or more (20 pounds if you weighed 200 to start), 36 percent had a reduction of 15 percent or more (30 pounds), and 18.4 percent had a reduction of 20 percent or more (40).
It’s hard to compare apples to apples here because the pills haven’t been put head-to-head in a clinical trial and in trials so far, the dosing and timing of the drugs is different. But just to paint the full picture, people taking 25 milligrams of oral semaglutide for 64 weeks lost roughly 13.6 percent of their body weight (27 pounds for the person who started at 200), per a clinical trial in The New England Journal of Medicine.
And, again, you can compare that to the max tolerated dose (1.7 mg or 2.4 mg) of injectable semaglutide, which, after 72 weeks results in roughly 13.7 percent weight loss (27.4 pounds). That’s according to a separate clinical trial in The New England Journal of Medicine. Meanwhile, the max tolerated dose (10 mg or 15 mg) of injectable tirzepatide resulted in roughly 20.2 percent of body weight (40.4 pounds) lost in the same time frame and per the same trial.
Looking ahead, 9mg of retatrutide for 68 weeks resulted in an average of 26.4 percent weight loss (52.8 pounds for a 200-pound person), per phase 3 clinical trials.
Why This Drug Is Noteworthy
“It’s important for several reasons,” Dr. Mehal says. For one, nearly all drugs people take today are small molecules. “By making a small molecule, it puts it in the same category as almost every other pill that we take,” he says. “If you take metformin or a diuretic or whatever, those are all small molecules.”
Second, this type of drug is cheaper to make, which may make them cheaper to buy. And third, peptides typically need to be refrigerated to some degree, but this pill will not require that.
How It Works
Foundayo works in a similar way to GLP-1s in that it binds to the same receptor, the GLP-1 receptor, and switches it on, Dr. Mehal says. “It’s a completely different key, but to the same lock,” he says. “Because it turns the same lock, the therapeutic effects and the side effect profile are very similar.”
Who Is the Best Candidate for This?
Foundayo may be helpful if:
• You don’t like injections (the Wegovy pill gets you around the needle, too, of course).
• You like simplicity. Oforglipron comes with a much simpler regimen than the first-to-market pill did. You don’t have to wait between when you swallow the pill and when you eat or drink. You do, however, still have to remember to take it every day.
•You’re looking to maintain weight you’ve lost on meds. One of the most exciting potential outcomes with the development of orforglipron, per Dr. Mehal, is that it may be effective for maintenance purposes, once someone already lost significant weight on an injectable. The benefit to this is that the pill will likely be less expensive and at a relatively lower dose, meaning fewer side effects.
What Else to Know About Orforglipron
Bigger picture, Dr. Mehal underscores that—as with all of these medicines—orforglipronworks best in conjunction with a healthy lifestyle, and determining the best medication for you should be discussed with your doctor.
Caitlin is a health and fitness journalist based in New York City. She writes for publications including The Wall Street Journal and Runner’s World. She’s completed 12 marathons, including the six World Marathon Majors, is semi-fluent in French, and volunteers as a greeter on The High Line. Follow her on Instagram or LinkedIn.
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