Tablets could offer a more convenient way to take weight-loss drugs
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A daily pill could soon be available as an alternative to Wegovy and Ozempic injections after a trial found it led to substantial weight loss and improved blood sugar levels in people with obesity and type 2 diabetes.
Orforglipron, developed by pharmaceutical company Eli Lilly, is designed to work similarly to semaglutide, the active ingredient in Wegovy and Ozempic, which mimics a hormone called GLP-1.
An earlier trial found that orforglipron helped people who were obese but without type 2 diabetes lose about 11% of their body weight, on average, over 72 weeks. That’s less than the 15 percent typically achieved over a similar period with injectable semaglutide, but taking the drug in pill form is more convenient, says Deborah Horn of the University of Texas.
To determine whether people with obesity and type 2 diabetes might also benefit, she and her colleagues recruited more than 1,600 people with both conditions in 10 countries, including India, Australia, China, Germany, Brazil and the United States.
They randomly assigned about 900 participants to take a low, medium, or high dose of orforglipron daily. The remaining participants took a placebo pill daily and all received lifestyle advice.
After 72 weeks, those who received the high dose had lost an average of almost 10 percent of their body weight, with 67 percent of this group losing more than 5 percent. The medium- and low-dose groups lost about 7 percent and 5 percent on average, while those on placebo lost less than 3 percent.
This confirms that orforglipron causes less weight loss than injectable GLP-1 drugs, but it may still provide benefits for people’s health and quality of life, says Stefan Trapp of University College London, who was not involved in the study. “A weight loss of just 5 percent tends to show very clear benefits: for example, people can do a little more exercise, change their lifestyle, reduce the risk of other diseases,” he says.
People taking the high dose also saw a reduction in their blood sugar levels of nearly 2 percent on average, with about 75 percent of them reaching the levels typically targeted by diabetic patients, Horn says. Lesser benefits were seen with lower doses, and those taking the placebo saw their blood sugar levels drop by just 0.1 percent.
About a tenth of participants who received high and medium doses had to stop taking the drug due to side effects such as nausea, vomiting and diarrhea, about twice the rate seen in the low-dose and placebo groups. But most participants found the side effects to be manageable, Horn says. “The side effects were consistent with those of other [injectable] GLP-1 drugs,” she says.
Eli Lilly hopes the drug will be approved by the U.S. Food and Drug Administration to treat obesity and Type 2 diabetes early next year, Horn said. “As a physician, I hope that the FDA will choose to 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.
Orforglipron should be cheaper to manufacture, store and deliver to patients than injectable GLP-1 drugs because it doesn’t require refrigeration or syringes, Trapp says. This, combined 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.
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