Daily pill could offer alternative to weight-loss injections

The daily tablet could soon become an alternative to Wegovy and Ozempic injections after a study found it led to significant weight loss and improved blood sugar levels in obese people with type 2 diabetes.

Orforgliprone, developed by pharmaceutical company Eli Lilly, works in the same way as semaglutide, the active ingredient in Wegovy and Ozempic, which mimics a hormone called GLP-1.

A preliminary trial found that orforgliprone allowed obese people without type 2 diabetes to lose about 11 percent of their body weight in an average of 72 weeks. This is less than the 15 percent typically achieved over the same period. with injectable semaglutidebut taking medications in tablet form is more convenient, he says Deborah Horn at the University of Texas.

To find out whether people with obesity and type 2 diabetes might also benefit, she and her colleagues enrolled more than 1,600 people with both diseases from 10 countries, including India, Australia, China, Germany, Brazil and the United States.

They randomly assigned about 900 participants to receive a low, medium, or high dose of orforgliprone daily. The remaining participants took a placebo pill daily and received lifestyle advice.

After 72 weeks, those taking the high dose lost an average of nearly 10 percent of their weight, with 67 percent of that group losing more than 5 percent. The medium- and low-dose groups lost an average of about 7 percent and 5 percent, while the placebo groups lost less than 3 percent.

This confirms that orforgliprone causes less weight loss than injectable GLP-1 drugs, but it may still provide benefits to people's health and quality of life, he says. Stefan Trapp at University College London, who was not involved in the study. “Losing just 5 percent of weight tends to show very clear benefits – for example, people can exercise a little more, change their lifestyle, reduce the risk of other diseases,” he says.

People taking high doses also saw their blood sugar levels drop by an average of nearly 2 percent, with about 75 percent of them reaching levels typically targeted for patients with diabetes, Horne says. Less benefit was seen at lower doses, and those taking the placebo saw their blood sugar levels drop by just 0.1 percent.

About a tenth of participants taking the high and medium doses had to stop taking the drug due to side effects such as nausea, vomiting and diarrhea, which was about twice as high as in the low-dose and placebo groups. But most participants found the side effects were manageable, Horne says. “Side effects were consistent with others [injectable] GLP-1 medications,” she says.

Eli Lilly hopes to have the drug approved by the U.S. Food and Drug Administration early next year to treat obesity and type 2 diabetes, Horne says. “As a physician, my hope is that the FDA will approve all three doses so that we have the flexibility to choose the best dose for our patients that optimizes health and minimizes side effects,” she says.

Orforgliprone should be cheaper to manufacture, store and deliver to patients than injectable GLP-1 drugs because it does not require refrigeration or syringes, Trapp says. This, coupled with the fact that it avoids the discomfort of injections, means it could expand access to GLP-1 weight-loss drugs, which are currently expensive and difficult to access in some low- and middle-income countries, he says.