If it seems like new medications for weight loss are coming out at a fast rate, that’s because. The first GLP-1 oral pills became available earlier this year. Now, a new oral GLP-1 from drug company Eli Lilly—called Foundayo (orforglipron)—has just won FDA approval.
Wajahat Mehal, MD, Medical Director of the Yale Center for Weight Management, said more options are on the way. Retatrutide, a so-called “triple agonist” will also be on the horizon later this year as well. In fact, Dr. Mehal believes that, eventually, there will be more than 15 different drugs to treat obesity. Some also explore 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 you need to know about Foundayo.
How Orforglipron Fits into the GLP-1 Landscape
First, lay the ground quickly. There are two peptides for weight loss currently in circulation: There is semaglutide (Ozempic, Wegovy) which activates the glucagon-like peptide-1 (GLP-1) receptor. Tirzepatide (Zepbound, Mounjaro) activates the same receptor as another called GIP (glucose-dependent insulinotropic polypeptide), making it slightly more effective for weight loss. Retatrutide, which has not yet been approved, activates two and a third. Until the beginning of this year, all these were only injected weekly.
The Wegovy pill came out in January making it the first oral GLP-1 formulation. Like the Wegovvy injection, it’s still semaglutide, and less effective in the oral formulation than the injectable (so, still less effective than tirzepatide, overall).
What makes Foundayo unique is that it is not 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 can be easier to use than the Wegovy pill, as there are no food or drink restrictions (more on that later).
While peptides are organic, biological compounds (like cheese or meat), small molecules are basically chemicals, which are more stable and easy and cheap to make, Dr. Mehal says.
How Effective Are the New Pills?
Clinical trials show that a new oral pill, orforglipron, will be comparable in effectiveness to oral semaglutide (Wegovy pills). Specifically, of the patients who took the highest dose-36 milligrams-of orforglipron for 72 weeks, 54.6 percent had reduced weight by 10 percent or more (20 pounds if weighed 200 to start), 36 percent had reduced 15 percent or more (30 pounds), and 18.4 percent more (20 percent).
It is difficult to compare apples to apples here because the pills have not been put into clinical trials and in the trials so far, the dosage and timing of the drugs are different. But just to paint the full picture, people who took 25 milligrams of oral semaglutide for 64 weeks lost about 13.6 percent of their body weight (27 pounds for people who started at 200), per a clinical trial at The New England Journal of Medicine.
And, again, you can compare it to the maximum tolerated dose (1.7 mg or 2.4 mg) of injectable semaglutide, which, after 72 weeks, caused a weight loss of 13.7 percent (27.4 pounds). That’s according to a separate clinical trial at The New England Journal of Medicine. Meanwhile, the maximum tolerated dose (10 mg or 15 mg) of injectable tirzepatide caused about 20.2 percent of body weight (40.4 pounds) to be lost during the same period 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 trial.
Why This Drug Is Noteworthy
“It’s important for several reasons,” said Dr. It’s expensive. For one, almost 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, it’s all small molecules.”
Second, these types of drugs are cheaper to make, which can make them cheaper to buy. And third, the peptide usually needs to be refrigerated to some degree, but this pill does 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 on, Dr. Mehal says. “It’s a different key, but it’s the same key,” he said. “Because it’s the same key, the therapeutic effects and the side effect profile are very similar.”
Who Are the Best Candidates for This?
Foundayo can help if:
• You do not like injections (the pills Wegovy get you around the needle, too, of course).
• You like simplicity. Oforglipron comes with a simpler regimen than the first pill to market. You should not wait between when you swallow the pill and when you eat or drink. However, you must remember to take it every day.
• You are looking to maintain the weight you have lost on meds. One of the most exciting potential results with the development of orforglipron, per Dr. Mehal, it can be effective for maintenance purposes, once someone has lost significant weight in the injectable. The advantage is that the pill will likely be cheaper and at a lower dose, meaning fewer side effects.
What else should I know about Orforglipron?
The bigger picture, Dr. Mehal emphasizes that—as with all these medications—orforglipron works best with a healthy lifestyle, and determining which medication is best for you should be discussed with your doctor.
Caitlin is a health and fitness reporter based in New York City. He writes for publications including The Wall Street Journal and Runner’s world. He has completed 12 marathons, including six World Marathon Majors, is semi-fluent in French, and volunteers as a greeter on The High Line. Follow him on Instagram or LinkedIn.
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