New Diabetes Pill Shows Promise in Blood Sugar and Weight Control

A new once-daily pill, orforglipron, developed by Eli Lilly, demonstrates significant potential in managing type 2 diabetes, offering comparable or even superior results to the oral version of semaglutide (Rybelsus) in reducing blood sugar levels and promoting weight loss, according to recent clinical trial findings.

Orforglipron vs. Oral Semaglutide: A Head-to-Head Comparison

The clinical trial, published in The Lancet, involved approximately 1,700 adults with type 2 diabetes. Participants were randomly assigned to receive either one of two doses of orforglipron or one of two doses of oral semaglutide. At the study’s outset, participants had an average A1C level of 8.3 percent, indicating suboptimal diabetes control.

After one year, those taking the higher dose of orforglipron experienced an average A1C reduction of 1.9 percent, compared to a 1.5 percent reduction in the higher-dose oral semaglutide group. Participants on the higher orforglipron dose too lost an average of almost 18 pounds (approximately 8 percent of their initial body weight), even as those on the higher dose of oral semaglutide lost an average of 11.5 pounds (a little over 5 percent of their starting weight). [1]

“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 and Discontinuation Rates

Both orforglipron and oral semaglutide are associated with common gastrointestinal side effects, including nausea, diarrhea, vomiting, and indigestion. However, a higher percentage of patients discontinued treatment with orforglipron compared to oral semaglutide. Approximately 10 percent of individuals taking the higher doses of orforglipron stopped treatment, compared to about 5 percent in the semaglutide group. [1]

Convenience and Flexibility with Orforglipron

A key advantage of orforglipron is its flexibility regarding meal timing. Unlike Rybelsus (oral semaglutide), which must be taken first thing in the morning on an empty stomach with a slight sip of water and requires a 30-minute waiting period before eating or drinking, orforglipron has no such restrictions. [1]

“This makes orforglipron easier to seize,” explains 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. Marilyn Tan, MD, a clinical professor at Stanford University School of Medicine, adds that this convenience is particularly beneficial for patients managing multiple medications.

How GLP-1 Drugs Work

Both orforglipron and oral semaglutide belong to a class of medications called GLP-1 (glucagon-like peptide-1) receptor agonists. These drugs mimic a natural hormone in the gut, which helps to suppress appetite and slow digestion, contributing to weight loss and improved blood sugar control. [1] They also stimulate insulin release in response to meals and reduce glucagon levels.

The American Diabetes Association generally recommends that adults with type 2 diabetes aim for A1C levels below 7 percent. Both doses of orforglipron and the higher dose of oral semaglutide achieved this target in the study, with the lower dose of semaglutide coming close, missing the goal by only 0.1 percent.

What’s Next for Orforglipron?

Eli Lilly plans to submit an application to the U.S. Food and Drug Administration (FDA) for approval of orforglipron as a treatment for type 2 diabetes. The company is also seeking approval for its use in obesity management, with an FDA decision expected in the spring of 2026. [2]

“These 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.