New GLP-1 Pill for Diabetes Shows Strong Results in Late-Stage Trial
People with type 2 diabetes had better blood sugar control and more weight loss with orforglipron than with oral semaglutide (Rybelsus) — but also more side effects.
An experimental GLP-1 pill may help people with type 2 diabetes reduce their blood sugar levels and body weight more than the oral version of Ozempic, according to the results of a new head-to-head clinical trial.
For the study, researchers randomly assigned roughly 1,700 adults with type 2 diabetes to take one of two doses of the new GLP-1 pill, orforglipron, or one of two doses of oral semaglutide. Oral semaglutide for diabetes is currently available under the brand name Rybelsus, and is sometimes referred to as Ozempic in a pill.
At the start of the study, all participants were struggling to manage their diabetes, with an average blood sugar A1C level of 8.3 percent.
After one year, participants taking the higher orforglipron dose saw their A1C levels drop by an average of 1.9 percent, according to results reported by drugmaker Eli Lilly. With the higher dose of oral semaglutide, A1C levels dropped by 1.5 percent.
Additionally, at the beginning of the study, the average participant weighed 214 pounds. By the end, people on the higher orforglipron dose lost almost 18 pounds, or about 8 percent of their starting weight. People on the higher dose of oral semaglutide lost less — 11.5 pounds on average, or a little more than 5 percent of their starting weight.
“So on efficacy alone, orforglipron looks better,” says Osama Hamdy, MD, PhD, an associate professor at Harvard Medical School and medical director of the Obesity Clinical Program at the Joslin Diabetes Center in Boston.
Side Effects Led More People to Stop Taking Orforglipron Than Its Rival Pill
With both GLP-1 pills, the most common side effects were gastrointestinal issues such as nausea, diarrhea, vomiting, and indigestion, per Lilly.
However, more patients discontinued treatment with orforglipron than with oral semaglutide in the new study. On the higher doses of these drugs, almost 10 percent of people taking orforglipron stopped treatment, compared with about 5 percent taking semaglutide.
The Experimental Pill Offers Extra Flexibility
One difference between these two GLP-1 pills has to do with timing around meals.
There are no restrictions on eating or drinking when people take orforglipron, per Lilly.
People on Rybelus, however, need to take it first thing in the morning, on an empty stomach, with just a small sip of water. To be effective, there can be no eating, drinking, or swallowing other pills for 30 minutes afterwards.
“This makes orforglipron easier to take,” says Melanie Jay, MD, a professor at the New York University Grossman School of Medicine and director of the NYU Langone Comprehensive Program on Obesity Research in New York City.
In particular, patients taking multiple medications may struggle to manage the timing with a semaglutide pill, finding orforglipron more convenient, says Marilyn Tan, MD, a clinical professor at Stanford University School of Medicine and chief of the endocrine clinic at Stanford Health Care in California.
“Adhering to a specific schedule of spacing out various medications can be cumbersome,” Dr. Tan says.
How GLP-1 Drugs Work for Diabetes
Both orforglipron and oral semaglutide are in a family of medicines known as GLP-1 (glucagon-like peptide-1) receptor agonists that work by mimicking a hormone in the gut that helps curb appetite and slow digestion. This can result in weight loss, which is associated with better blood sugar control.
In addition, GLP-1 drugs increase the release of the hormone insulin in response to meals, which help lower blood sugar. GLP-1 drugs also reduce levels of the hormone glucagon, which can raise blood sugar.
The goal for adults with type 2 diabetes is to get A1C levels below 7 percent. Both doses of orforglipron and the higher dose of the semaglutide pill hit this target in the study, and the lower-dose semaglutide pill dose missed this goal by just 0.1 percent.
The new study results “give us further reassurance that both orforglipron and semaglutide are excellent medications to treat type 2 diabetes,” says Beverly Tchang, MD, an associate professor of clinical medicine at the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City.
When Will Orforglipron Be Available?
Lilly said it plans to apply for U.S. Food and Drug Administration (FDA) approval of oforglipron as a diabetes treatment “as soon as possible.” The company is already pursuing approval of orforglipron for obesity, and expects a decision from the FDA this spring.
EDITORIAL SOURCES
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Resources
Lilly’s Oral GLP-1, Orforglipron, Delivered Superior Blood Sugar Control and Weight Loss Compared to Oral Semaglutide in Head-to-Head Type 2 Diabetes Trial Published in The Lancet. Eli Lilly. February 26, 2024.
Tom Gavin joined Everyday Health as copy chief in 2022 after a lengthy stint as a freelance copy editor. He has a bachelor's degree in psychology from College of the Holy Cross.
Prior to working for Everyday Health, he wrote, edited, copy edited, and fact-checked for books, magazines, and digital content covering a range of topics, including women's health, lifestyle, recipes, restaurant reviews, travel, and more. His clients have included Frommer's, Time-Life, and Google, among others.
He lives in Brooklyn, New York, where he likes to spend his time making music, fixing too-old electronics, and having fun with his family and the dog who has taken up residence in their home.
Lisa Rapaport is a journalist with more than 20 years of experience on the health beat as a writer and editor. She holds a master’s degree from the UC Berkeley Graduate School of Journalism and spent a year as a Knight-Wallace journalism fellow at the University of Michigan. Her work has appeared in dozens of local and national media outlets, including Reuters, Bloomberg, WNYC, The Washington Post,Los Angeles Times, Scientific American, San Jose Mercury News, Oakland Tribune, Huffington Post, Yahoo! News, The Sacramento Bee, and The Buffalo News.
